No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Role of apparent diffusion coefficient values for the differentiation of viable and necrotic areas of breast cancer and its potential utility to vide voxel positioning for MRS in the absence of dynamic contrast-enhanced MRI data
Abstract
We carried out retrospective analysis of apparent diffusion coefficient (ADC) values in 48 infiltrating ductal breast cancer patients who had dynamic contrast-enhanced magnetic resonance imaging (DCEMRI; Group I) and in 53 patients (Group II) for whom DCEMRI data were not available. Twenty-three patients of Group I showed no necrosis (Group Ia), while in 25 patients, both viable (nonnecrotic) and necrotic tumor areas (Group Ib) were observed on DCEMRI. T1-weighted, fat-suppressed and short inversion recovery images were used to identify the viable and necrotic tumor areas in Group II patients, and necrosis was not seen in 11 patients (Group IIa), while 42 (Group IIb) showed both viable and necrotic tumor areas. The ADCs of the necrotic area of Group Ib (1.79±0.30 ×10(-3) mm(2)/s) and Group IIb (1.83±0.40 ×10(-3) mm(2)/s) patients were similar and significantly higher (P<.01) compared to the ADCs of the viable tumor area of Group Ia (0.96±0.21 ×10(-3) mm(2)/s) and Group IIa (0.90±0.17 ×10(-3) mm(2)/s) patients. Proton MR spectroscopy (MRS) data were also available in these patients, and the ADC values were retrospectively determined from the voxel from which MR spectrum was obtained. These values were compared with the ADC obtained for the viable and necrotic areas of the tumor. ADC of the MRS voxel was similar to that obtained for the viable tumor area in patients of both groups. This interesting observation reveals the potential utility of using ADC values to identify viable tumor area for positioning of voxel for MRS in the absence of DCEMRI data.
... The 1H-MRS sequence was acquired via using the following technical parameters; repetition time (TR) = 2000 ms (msec.); echo time (TE) = 270 ms; flip In all patients to obtain MRS measurements of the breast lesions and to avoid a contamination signal from the normal breast tissue, the localized voxel of interest (VOI) was placed in the center of the viable area of the tumor (to differentiate viable from necrotic regions), using ADC values, which are useful parameters to guide voxel positioning for 1H-MRS instead of DCE-MRI images) [10]. ...
... Spectral lipid suppression was achieved using a bandwidth of 1.8 ppm (ppm) with start and end frequencies for the fat region of 2.2 ppm and 0.4 ppm, respectively. In addition, outer volume suppression was achieved by the use of 4-6 saturation bands [10]. ...
... A threshold signal-tonoise ratio (SNR) of 2 or more was utilized for tCho peak [11,12]. Also, as described elsewhere [5,10], the automated normalization with an internal water reference scan of the post-processing software, was used to calculate the tCho concentration. ...
Aim of the work
To study the diagnostic performance of combined single voxel 1H-MRS and DW-MRI with ADC values as a non-contrast diagnostic tool, compared to the DCE-MRI, in suspicious breast lesions.
Materials and methods
113 female patients (mean age 45.8 years) with suspicious breast lesions, categorized as BI-RADS 3 or 4 by sono-mammographic examinations, were subjected to bilateral breast imaging with non-contrast MRI including conventional MRI, DW-MRI with quantitative ADC values, and single voxel 1H-MRS, in addition to DCE-MRI. They had 132 pathologically proved lesions (74 benign and 58 malignant).
Results
DW-MRI with ADC values was 96.97% accurate with 94.92% sensitivity and 98.63% specificity, while DCE-MRI was 97.73% accurate with 98.29% sensitivity but with 97.29% specificity, and 1H-MRS was 98.48% accurate with the highest sensitivity (100%) and 97.33% specificity. Furthermore, the combined use of DW-MRI with ADC values and 1H-MRS improved the diagnostic capability than utilization of each sequence alone with the highest accuracy of 99.24%, 100% sensitivity and 98.65% specificity.
Conclusion
The combined use of DW-MRI with quantitative ADC data and single-voxel 1H-MRS is a reliable non-contrast tool that provides higher accuracy in characterizing suspicious breast, and can efficiently be used in the absence of DCE-MRI.
... It has also been reported that DWI of breast in combination with T2-weighted imaging has the potential to improve the specificity of breast cancer diagnosis (17). However in our study, three IDC patients with AJCC stage III A and with Type III curve showed an ADC value which was above the cutoff, which may be attributed to the intermingling necrotic cores seen in such large sized tumors (44). ...
... Further, EBC had a higher tCho concentration compared to LABC, indicating more necrotic cores in LABC (49). In an earlier study, ADC was used to delineate necrotic and viable regions using DWI in patients who cannot afford the cost of contrast (44). In the calculation of ADC, the visible hyperintense necrotic areas were avoided; however, there is a possibility that intermingling microsized necrotic regions might have been included in the ROIs, especially in large tumors, which might have led to higher ADC seen in LABC patients. ...
The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 x 10-3 mm2/s) compared to benign (1.57 ± 0.26 x 10-3 mm2/s) and healthy (1.78 ± 0.13 x 10-3 mm2/s) breast tissues. A cut-off ADC value of 1.23 x 10-3 mm2/s (sensitivity 92.5%; specificity 91.1%; AUC 0.96) to differentiate malignant from benign diseases was arrived by ROC analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen while their ADC value showed as positive for malignancy implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with the tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor (HER2)] and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA; IIB and IIIA; and IIB and III (B + C) (p
... 22 Recent technical improvements in voxel positioning and measuring ADC in breast tumors have been reported. 23 Nevertheless, there are still many caveats regarding the cut points and recording parameters that may influence the accuracy with which benign and cancerous breast lesions are distinguished from each other using DWI. 21,23 Molecular Imaging Through MR for Identifying Breast Cancer ...
... 23 Nevertheless, there are still many caveats regarding the cut points and recording parameters that may influence the accuracy with which benign and cancerous breast lesions are distinguished from each other using DWI. 21,23 Molecular Imaging Through MR for Identifying Breast Cancer ...
Magnetic resonance (MR)-based modalities aid breast cancer detection without exposure to ionizing radiation. Magnetic resonance imaging is very sensitive but costly and insufficiently specific. Molecular imaging through magnetic resonance spectroscopy (MRS) can provide information about key metabolites. Here, the measured/encoded time signals cannot be interpreted directly, necessitating mathematics for mapping to the more manageable frequency domain. Conventional applications of MRS are hampered by data analysis via the fast Fourier transform (FFT) and postprocessing by fitting techniques. Most in vivo MRS studies on breast cancer rely upon estimations of total choline (tCHO). These have yielded only incremental improvements in diagnostic accuracy. In vitro studies reveal richer metabolic information for identifying breast cancer, particularly in closely overlapping components of tCHO. Among these are phosphocholine (PC), a marker of malignant transformation of the breast. The FFT cannot assess these congested spectral components. This can be done by the fast Padé transform (FPT), a high-resolution, quantification-equipped method, which we presently apply to noisy MRS time signals consistent with those encoded in breast cancer. The FPT unequivocally and robustly extracted the concentrations of all physical metabolites, including PC. In sharp contrast, the FFT produced a rough envelope spectrum with a few distorted peaks and key metabolites absent altogether. As such, the FFT has poor resolution for these typical MRS time signals from breast cancer. Hence, based on Fourier-estimated envelope spectra, tCHO estimates are unreliable. Using even truncated time signals, the FPT clearly distinguishes noise from true metabolites whose concentrations are accurately extracted. The high resolution of the FPT translates directly into shortened examination time of the patient. These capabilities strongly suggest that by applying the FPT to time signals encoded in vivo from the breast, MRS will, at last, fulfill its potential to become a clinically reliable, cost-effective method for breast cancer detection, including screening/surveillance.
... Although such incidences are low, it is associated with poor prognosis (4). Moreover, previous studies have also shown that PABC usually manifests at more advanced stage, with larger tumors and higher incidence of lymph node metastasis (5)(6)(7)(8). Evaluation of breast cancer using conventional mammography is often difficult during pregnancy and lactation due to the increased parenchymal and glandular content in the breast (9,10). Various MR methods have been explored in the differentiation of malignant from benign breast lesions (11)(12)(13). ...
... In vivo single voxel 1 H MRS experiments were carried out using a point-resolved spin-echo sequence (PRESS) in all subjects with the following parameters: TR ¼ 1500 ms; TE ¼ 100 ms; averages ¼ 128; spectral width ¼ 1000 Hz; vector size ¼ 1024; with a total acquisition time of 3.18 min. A voxel of size 20 Â 20 Â 20 mm 3 was positioned well within the viable tumor using ADC values (to differentiate viable from necrotic regions) (8) in all patients, while in lactating women volunteers the voxel was positioned in the clearly visible hyperintense fibroglandular tissue of T2 fat suppressed MR images. Both global and voxel level 36 pre T3N1M0, stage IIIA IDC *T ¼ tumor; N ¼ lymph node; M ¼ metastasis; T3/T4 ¼ size and/or extension of the primary tumor; N0 ¼ tumor cells absent from regional lymph nodes; N1 ¼ regional lymph node metastasis present; (at some sites: tumor spread to closest or small number of regional lymph nodes); N2 ¼ tumor spread to an extent between N1 and N3; N3 ¼ tumor spread to more distant or numerous regional lymph nodes; M0 ¼ no distant metastasis; IDC ¼ infiltrating ductal carcinoma magnetic field shimming was carried out manually and the line-width of water resonance peak for the voxel ranged from 8 to 20 Hz in the patients with breast cancer. ...
To investigate the potential of diffusion weighted imaging (DWI) and in vivo proton MR spectroscopy (MRS) in the differentiation of breast tissue of healthy lactating women volunteers and breast cancer patients.
DWI and MRS were carried out at 1.5 Tesla on 12 breast cancer patients and 12 normal lactating women volunteers. Apparent diffusion coefficient (ADC) and total choline (tCho) concentration were determined.
tCho was observed in all breast cancer patients and in 10/12 lactating women. Additionally a peak at 3.8 ppm corresponding to lactose was seen in 10/12 of lactating women. Concentration of tCho was similar in malignant breast tissue of patients (3.51 ± 1.72 mmol/kg) and in normal breast tissue of lactating women (3.52 ± 1.70 mmol/kg). However, ADC was significantly higher in the normal breast tissue of lactating women (1.62 ± 0.22 × 10(-3) mm(2) /s) compared with the malignant breast tissue of patients (1.01 ± 0.10 × 10(-3) mm(2) /s).
Observation of lactose peak with higher ADC in the breast tissue of healthy lactating women volunteers may aid in differentiation of changes that occur in breast tissue due to normal physiological conditions like lactation compared with malignant transformation. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
... For characterization of breast lesions into malignant and benign using ADC values, several groups have reported a sensitivity and specificity of 93% and 88%, respectively ( Guo et al. 2002;Jin G et al. 2010). Sharma et al also reported the role of DWI for the differentiation of viable and necrotic areas of breast cancer and its potential utility to guide voxel positioning for MRS in the absence of dynamic contrast-enhanced MRI data ( Sharma et al. 2012). The usefulness of ADC values to differentiate non-responders from responders as early as the first cycle of NACT compared to the tumor diameter ( Sharma et al. 2009, Agrawal et al. 2017). ...
... The rate of diffusion in tissue is described by an apparent diffusion coefficient (ADC), which can be measured by established DW-MRI methods (17)(18)(19)(20). In controlled experiments the variations in ADC have been shown to correlate inversely with tissue cellularity (21)(22)(23)(24)(25). ...
Pathologic complete response following neoadjuvant therapy (NAT) is used as a short-term surrogate marker of eventual outcome in patients with breast cancer. Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained before and after the first cycle of NAT ([Formula: see text]), in conjunction with receptor status, may improve the predictive accuracy of tumor response to NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent diffusion coefficient and efflux rate constant, with receptor status in a logistic ridge-regression model. The area under the curve (AUC) and Brier score of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99) and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly support the hypothesis that our proposed model outperforms the other models that we investigated (namely, models without either receptor information or voxel-level information). The contribution of the receptor information was manifested by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These data indicate that combining multiparametric MRI with hormone receptor status has a high likelihood of improved prediction of pathologic response to NAT in breast cancer.
... For MRS data acquisition, a single voxel (range of 10 × 10 × 10 to 10 × 35 × 45 mm 3 depending on the tumor size) was placed on the reference MR images by carefully avoiding the necrotic areas of the tumor. In vivo 1 H MRS was carried out by localizing the voxel on the visible tumor carefully avoiding the necrotic areas using the T2W Fat Sat (fat saturated) and diffusion weighted images 64 . The restricted hypointense appearing viable areas and the hyperintense areas with dead cells could be well differentiated on a lesion using apparent diffusion coefficient (ADC) maps which helps in proper voxel positiong during MRS acquisition by avoiding the dead necrotic areas. ...
... Partridge et al. [200] appraised the effect of intravoxel fat signal on ADC measurement and found that robust fat suppression was significant for efficient ADC measurement. Sharma et al. [201] assessed the role of ADC values for distinguishing of viable and necrotic areas of breast carcinoma and found inferior ADC value at tumor area. Costantini et al. [202] analyzed that ADC value showed distinctive variation in tumors, which were 0.96 10x -3 mm 2 /s for aggressive tumors and 1.19 10x -3 mm 2 /s for less aggressive tumors. ...
Background: Breast carcinoma is a life threatening disease that accounts for 25.1% of all carcinoma among women worldwide. Early detection of the disease enhances the chance for survival.
Discussion: This paper presents comprehensive report on breast carcinoma disease and its modalities available for detection and diagnosis, as it delves into the screening and detection modalities with special focus placed on the non-invasive techniques and its recent advancement work done, as well as a proposal on a novel method for the application of early breast carcinoma detection.
Conclusion: This paper aims to serve as a foundation guidance for the reader to attain bird’s eye understanding on breast carcinoma disease and its current non-invasive modalities.
... For MRS data acquisition, a single voxel (range of 10 × 10 × 10 to 10 × 35 × 45 mm 3 depending on the tumor size) was placed on the reference MR images by carefully avoiding the necrotic areas of the tumor. In vivo 1 H MRS was carried out by localizing the voxel on the visible tumor carefully avoiding the necrotic areas using the T2W Fat Sat (fat saturated) and diffusion weighted images 64 . The restricted hypointense appearing viable areas and the hyperintense areas with dead cells could be well differentiated on a lesion using apparent diffusion coefficient (ADC) maps which helps in proper voxel positiong during MRS acquisition by avoiding the dead necrotic areas. ...
Total choline (tCho) was documented as a biomarker for breast cancer diagnosis by in vivo MRS. To understand the molecular mechanisms behind elevated tCho in breast cancer, an association of tCho with β-catenin and cyclin D1 was evaluated. Hundred fractions from 20 malignant, 10 benign and 20 non-involved breast tissues were isolated. Cytosolic and nuclear expressions of β-catenin and cyclin D1 were estimated using ELISA. Higher tCho was seen in malignant compared to benign tissues. Malignant tissues showed higher cytosolic and nuclear β-catenin expressions than benign and non-involved tissues. Within malignant tissues, β-catenin and cyclin D1 expressions were higher in the nucleus than cytosol. Cyclin D1 expression was higher in the cytosolic fractions of benign and non-involved than malignant tissues. Furthermore, in malignant tissues, tCho showed a positive correlation with the cytosolic and nuclear expression of β-catenin and cyclin D1 and also a correlation between nuclear expressions of both these proteins was seen. Higher cytosolic β-catenin expression was seen in progesterone receptor negative than positive patients. Results provide an evidence of correlation between non-invasive biomarker, tCho and the Wnt/β-catenin pathway. The findings explain the molecular mechanism of tCho elevation which may facilitate exploration of additional therapeutic targets for breast cancer.
... 1 Derived apparent diffusion coefficient (ADC) values can facilitate differentiation of malignant and benign breast lesions [2][3][4] and identify early response to neoadjuvant chemotherapy in breast cancer. [5][6][7][8] First used in the breast in 1997, 9 ADC's clinical utility is increasing as it has been shown to improve the diagnostic specificity and positive predictive value of dynamic contrast enhanced (DCE)-MRI. 10,11 A standard single-shot echoplanar sequence is the most widely used technique using b values of 0 to 1000 s/mm 2 with at least three b values to ensure robustness and reproducibility 4,11,12 and can be obtained in a few minutes. ...
Purpose:
To evaluate the diagnostic sensitivity of computed diffusion-weighted (DW)-MR imaging for the detection of breast cancer.
Materials and methods:
Local research ethics approval was obtained. A total of 61 women (median 48 years) underwent dynamic contrast enhanced (DCE)- and DW-MR between January 2011 and March 2012, including 27 with breast cancer on core biopsy and 34 normal cases. Standard ADC maps using all four b values (0, 350, 700, 1150) were used to generate computed DW-MR images at b = 1500 s/mm(2) and b = 2000 s/mm(2) . Four image sets were read sequentially by two readers: acquired b = 1150 s/mm(2) , computed b = 1500 s/mm(2) and b = 2000 s/mm(2) , and DCE-MR at an early time point. Cancer detection was rated using a five-point scale; image quality and background suppression were rated using a four-point scale. The diagnostic sensitivity for breast cancer detection was compared using the McNemar test and inter-reader agreement with a Kappa value.
Results:
Computed DW-MR resulted in higher overall diagnostic sensitivity with b = 2000 s/mm(2) having a mean diagnostic sensitivity of 76% (range 49.8-93.7%) and b = 1500 s/mm(2) having a mean diagnostic sensitivity of 70.3% (range 32-97.7%) compared with 44.4% (range 25.5-64.7%) for acquired b = 1150 s/mm(2) (both p = 0.0001). Computed DW-MR images produced better image quality and background suppression (mean scores for both readers: 2.55 and 2.9 for b 1500 s/mm(2) ; 2.55 and 3.15 for b 2000 s/mm(2) , respectively) than the acquired b value 1150 s/mm(2) images (mean scores for both readers: 2.4 and 2.45, respectively).
Conclusion:
Computed DW-MR imaging has the potential to improve the diagnostic sensitivity of breast cancer detection compared to acquired DW-MR. J. Magn. Reson. Imaging 2016.
... Despite technical advances that aid in voxel positioning and measuring ADC in breast tumors [57], problems remain, however, in selecting cutpoints and optimal recording parameters for DWI. Thus, benign and malignant breast lesions and prediction/assessment of response to therapy cannot yet be distinguished using DWI with sufficient confidence [49,58]. ...
We comprehensively examine the performance of the fast Padé transform (FPT) for handling noise-corrupted magnetic resonance spectroscopic (MRS) data from normal breast, fibroadenoma and breast cancer in the controlled setting compared to conventional processing through the fast Fourier transform (FFT) for a wide chemical shift region. Included is an assessment of the performance of the (Formula presented.) for very heavily noise-corrupted MRS time signals from the breast. For all three categories of breast tissue, the FFT produced only rudimentary total shape spectra with coarse, broad, shortened peaks at full signal length, whereas the (Formula presented.) fully resolved all the tightly-packed, and some completely overlapping resonances, accurately reconstructing the spectral parameters from which all the metabolite concentrations were exactly computed. With added noise of standard deviation (Formula presented.) root-mean-square, the (Formula presented.) clearly identified and exactly reconstructed all the genuine resonances and distinguished these from the much more abundant spurious content. The powerful capability of the (Formula presented.) to induce convergence into divergent series via analytical continuation appears to result in more noise cancellation, with pole–zero coincidence remaining complete even at very high noise levels. These results represent a critical step towards efficient in vivo implementations of MRS, where there is no input data with which to check. Detailed consideration is made of how these results could improve the diagnostic yield of MRS for breast cancer, and how this could potentially impact upon a more personalized approach to care of patients afflicted with or at risk for this malignancy.
... The Correlation of PET/MRI at the Molecular Level possibility of discrimination of necrotic and nonnecrotic tissue is already well described. 13,14 Previous studies have shown that [ 18 F]FDG PET and diffusion-weighted imaging can be used as a predictor of tumor necrosis staging in histology. 15 Furthermore, a study by Jung and colleagues showed that the ADC values correlated with the degree of intratumoral necrosis on pathologic slides in a prostate cancer xenograft mouse model. ...
We aimed to quantitatively characterize the treatment effects of docetaxel in the HCT116 xenograft mouse model, applying diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and 3'-deoxy-3'-[18F]-fluorothymidine ([18F]FLT). Mice were imaged at four time points over 8 days. Docetaxel (15 mg/kg) was administered after a baseline scan. Voxel-wise scatterplots of PET and apparent diffusion coefficient (ADC) data of tumor volumes were evaluated with a threshold cluster analysis and compared to histology (GLUT1, GLUT3, Ki67, activated caspase 3a). Compared to the extensive tumor growth observed in the vehicle-treated group (from 0.32 ± 0.21 cm3 to 0.69 ± 0.40 cm3), the administration of docetaxel led to tumor growth stasis (from 0.32 ± 0.20 cm3 to 0.45 ± 0.23 cm3). The [18F]FDG/ADC cluster analysis and the evaluation of peak histogram values revealed a significant treatment effect matching histology as opposed to [18F]FLT/ADC. [18F]FLT uptake and the Ki67 index were not in good agreement. Our voxel-based cluster analysis uncovered treatment effects not seen in the separate inspection of PET and MRI data and may be used as an independent analysis tool. [18F]FLT/ADC cluster analysis could still point out the treatment effect; however, [18F]FDG/ADC reflected the histology findings in higher agreement.
... Partridge et al 54 combined DW-MRI with DCE-MRI wash-out kinetics with strong indications that their method improved accuracy of making the diagnosis. The authors are in agreement that the combination of DW and DCE-MRI increases the specificity for detection.In a recent study, Sharma et al55 show the potential of using ADC values to identify viable tumor areas for voxel positioning in MRS without DCE-MRI data being available. The authors used ADC values to differentiate between necrotic and viable tumor regions in breast cancer patients. ...
Breast cancer incidence is increasing worldwide. Early detection is critical for long-term patient survival, as is monitoring responses to chemotherapy for management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS) has gained in importance in the last decade for the diagnosis and monitoring of breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is very high and the consensus is that MRI is more sensitive in detection than x-ray mammography. Advantages of MRS include delivery of biochemical information about tumor metabolism, which can potentially assist in the staging of cancers and monitoring responses to treatment. The roles of MRS and MRI in screening and monitoring responses to treatment of breast cancer are reviewed here. We rationalize how it is that different histological types of breast cancer are differentially detected and characterized by MR methods.
In the last two decades, various in vivo MR methodologies have been evaluated for their potential in the study of cancer metabolism. During malignant transformation, metabolic alterations occur, leading to morphological and functional changes. Among various MR methods, in vivo MRS has been extensively used in breast cancer to study the metabolism of cells, tissues or whole organs. It provides biochemical information at the metabolite level. Altered choline, phospholipid and energy metabolism has been documented using proton (¹H), phosphorus (³¹P) and carbon (¹³C) isotopes. Increased levels of choline‐containing compounds, phosphomonoesters and phosphodiesters in breast cancer, which are indicative of altered choline and phospholipid metabolism, have been reported using in vivo, in vitro and ex vivo NMR studies. These changes are reversed on successful therapy, which depends on the treatment regimen given. Monitoring the various tumor intermediary metabolic pathways using nuclear spin hyperpolarization of ¹³C‐labeled substrates by dynamic nuclear polarization has also been recently reported. Furthermore, the utility of various methods such as diffusion, dynamic contrast and perfusion MRI have also been evaluated to study breast tumor metabolism. Parameters such as tumor volume, apparent diffusion coefficient, volume transfer coefficient and extracellular volume ratio are estimated. These parameters provide information on the changes in tumor microstructure, microenvironment, abnormal vasculature, permeability and grade of the tumor. Such changes seen during cancer progression are due to alterations in the tumor metabolism, leading to changes in cell architecture. Due to architectural changes, the tissue mechanical properties are altered; this can be studied using magnetic resonance elastography, which measures the elastic properties of tissues. Moreover, these structural MRI methods can be used to investigate the effect of therapy‐induced changes in tumor characteristics. This review discusses the potential of various in vivo MR methodologies in the study of breast cancer metabolism.
An approach using direct regularization from coregistered DCE-MR images (DRI) was used to reconstruct Near- Infrared Spectral Tomography (NIRST) patient images, which does not need image segmentation. Twenty patients with mammography/ultrasound confirmed breast abnormalities were involved in this study, and the resulting images indicated that tumor HbT contrast differentiated malignant from benign cases (p-value=0.021). The approach produced reconstructed images which significantly reduced surface artifacts near the sourcedetector locations (p-value=4.16e-6).
Purpose
To compare the diagnostic performance of Diffusion Weighted Imaging (DWI) acquired with 1.5T and 3.0T magnetic resonance (MR) units in differentiating malignant breast lesions from benign ones.
Materials and Methods
A comprehensive search of the PubMed and Embase databases was performed on articles published from January 01, 2000, to February 19, 2016. The quality of the included studies was assessed. Statistical analysis included pooling of diagnostic sensitivity and specificity and assessing data inhomogeneity and publication bias.
Results
A total of 61 studies were included after full-text review, which included 4778 patients and 5205 breast lesions. The overall sensitivity and specificity were 90% (95% CI, 88%-92%) and 86% (95% CI, 82%-89%). The pooled diagnostic odds ratios (DORs) were 53 (95% CI, 37-74). For breast cancers versus benign lesions, the area under the curve (AUC) was 0.94 (95% CI, 0.92-0.96). For the 41 studies that used a 1.5T MR unit, the pooled sensitivity and specificity were 91% (95% CI, 89%-92%) and 86% (95% CI, 81%-90%). For the 17 studies that used a 3.0T MR unit, the pooled sensitivity and specificity were 88% (95% CI, 83%-91%) and 84% (95% CI, 0.78-0.89). Publication bias and significant heterogeneity were observed, but no threshold was found among the 61 studies. No significant difference was found in the sensitivity or specificity between the subgroups.
Conclusion
The comparison between the subgroups that separately used 1.5T or 3.0T MR units suggested that the diagnostic accuracy for breast cancers compared to benign lesions was not significantly different.
Purpose:
The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated.
Methods:
DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADCWT), solid tumor (ADCST), intra-tumoral necrosis (ADCNec) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins.
Results:
Of 38 patients, 6 were pathological complete (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADCST and ADCWT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of the outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR indicating the presence of residual disease in these shells.
Conclusion:
This pre-surgery information may serve as a guide to define cancer free margins and extent of residual disease which may be useful in planning breast conservation surgery.
We apply the fast Padé transform (FPT) to time signals as encoded via magnetic resonance spectroscopy (MRS) in breast fibroadenoma. Realistic levels of noise are considered. The conventional fast Fourier transform (FFT) is also used for comparison with the FPT. For \(N = 2048\) signal points, the FFT generated uninformative total shape spectra with only a few distorted peaks, whereas the FPT yielded converged envelope spectra at partial signal length \(N_\mathrm{P}= 1700\) . To match the FPT based at time signals sampled at \(N = 2048\) , the FFT requires \(N = 65536\) signal points, i.e. a 32-fold lengthening of each transient. Via the parametric FPT, at \(N_\mathrm{P} = 1700\) all the resonances were resolved and metabolite concentrations precisely computed, including those that were almost completely overlapping (phosphocholine and phosphoethanolamine whose chemical shifts are separated by 0.001 parts per million). The multi-faceted signal–noise separation (SNS) procedure was applied through identification of pole-zero cancellations, zero or near zero amplitudes plus the stability test against different levels of noise. Via SNS, all the spurious resonances were confidently identified, thus leaving only genuine metabolites in the output list. Practical implications are underscored: the high resolution of the FPT will shorten the examination time of the patient. Using the FPT, the cancer biomarker phosphocholine, plus other informative metabolites can be identified and their concentrations exactly determined. Applying the fast Padé transform to time signals encoded in vivo from the breast therefore will be a key step for MRS to realize its potential to become a reliable, cost-effective method for breast cancer diagnostics.
Magnetic resonance imaging (MRI) has high sensitivity but low specificity for breast cancer, and consequently, new techniques to improve the specificity of breast MRI in diagnosing breast cancer are under development.
To assess the ability of the apparent diffusion coefficient (ADC) compared with the ADC ratio (ADCr) to differentially diagnose benign compared with malignant breast lesions.
Forty-eight women with breast lesions (average age, 45 years) underwent MRI scanning including T1-weighted dynamic contrast-enhanced (DCE) scanning and diffusion-weighted imaging (DWI). The average ADC and ADCr values for both lesions and pectoralis major muscles (ADCrmuscle and ADCrmuscle) were measured in patients with malignant (n = 25) and benign (n = 23) breast lesions. The ADCr of the contralateral breast (ADCr contralateral) was also evaluated. All histology was confirmed by pathological analysis of biopsied tissue. ADC and ADCr values were analyzed using receiver-operating characteristic (ROC) curves.
For benign lesions compared with malignant lesions, lesion-side ADC was 1.45 vs. 1.05, respectively (P < 0.001), normal-side ADC was 1.82 vs.1.64 (P = 0.002), ADCrmuscle was 1.35 vs. 0.9 (P < 0.001), and ADCrcontralateral was 0.79 vs. 0.64 (P = 0.001). ADCrmuscle showed higher sensitivity (82.61%) and specificity (96.00%) than ADCrcontralateral (60.87% and 92.00%, respectively) and ADC (69.57% and 96.00%) for discriminating malignant from benign lesions. The AUC using ADCrmuscle had higher discriminatory power (0.92, P < 0.001) for malignant versus benign breast lesions compared with either ADC (0.82, P < 0.001) or ADCrcontralateral (0.78, P = 0.001).
The ADCrmuscle value showed higher sensitivity and specificity and improved diagnostic accuracy compared with either ADC or ADCrcontralateral in differentiating benign from malignant breast lesions.
© The Foundation Acta Radiologica 2015.
Diffusion-weighted imaging (DWI) of the breast provides additional contrast information in breast magnetic resonance imaging (MRI). The DWI procedure can easily be implemented in the routine breast MRI protocol with little time expenditure regarding image acquisition and evaluation. Evaluation of the DW images can be performed with or without the routine breast MRI sequences (T2w and T1w with contrast material) but evaluation in combination with the routine program is highly recommended. Objective analysis of the tissue diffusion can be achieved by calculating the apparent diffusion coefficient (ADC) value with the scanner software. The choice of the DW sequence, evaluation and determination of the ADC threshold to differentiate between benign and malignant lesions should be scanner adapted. The use of DW imaging qualifies for routine use regarding the differentiation between malignant and benign breast lesions. Non-mass-like lesions and monitoring neoadjuvant chemotherapy can also be evaluated with DW sequences. The benefit of the additional information from DW-MR mammography to characterize non-mass-like lesions and in the course of neoadjuvant chemotherapy remains unclear to date.
To document the apparent diffusion coefficient (ADC) of fibroglandular breast tissue in women at high-risk of developing breast cancer and investigate the relationship between ADC and breast density.
Local research ethics approval was obtained. A total of 33 high-risk women including 17 BRCA1/2 mutation carriers (mean age, 43 years) and 16 women postmantle irradiation (mean age 40 years) underwent diffusion-weighted MRI between days 6 and 16 of their menstrual cycle. ADC histograms from a region of interest in fibroglandular tissue and mammographic breast density measurements were obtained. Mean, percentile ADC values (10th, 25th, 50th, 75th, 90th) and skew were compared for the two groups; ADC and mammographic breast density were correlated.
Mean ADC values (×10(-6) mm(2) /s) were 2017 ± 197 in postmantle irradiated women and 1827 ± 289 in BRCA1/2 mutation carriers (P = 0.035) with significant differences at all percentiles (P < 0.0001) but not skew (P = 0.44). ADC values showed weak positive correlation with mammographic breast density in BRCA1/2 mutation carriers (r = 0.51, P = 0.043) but not in postmantle radiotherapy patients (r = 0.49, P = 0.13).
Higher ADC values seen in fibroglandular tissue postmantle irradiation compared with BRCA1/2 mutation carriers has potential to improve tumor detection in these patients. Lack of correlation between ADC and breast density postmantle irradiation may be a result of microstructural changes.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
The purpose of this study was to evaluate whether texture‐based analysis of standard MRI sequences and diffusion‐weighted imaging can help in the discrimination of parotid gland masses.
The MR images of 38 patients with a biopsy‐ or surgery‐proven parotid gland mass were retrospectively analyzed. All patients were examined on the same 3.0 Tesla MR unit, with one standard protocol. The ADC (apparent diffusion coefficient) values of the tumors were measured with three regions of interest (ROIs) covering the entire tumor. Texture‐based analysis was performed with the texture analysis software MaZda (version 4.7), with ROI measurements covering the entire tumor in three slices. COC (co‐occurrence matrix), RUN (run‐length matrix), GRA (gradient), ARM (auto‐regressive model), and WAV (wavelet transform) features were calculated for all ROIs. Three subsets of 10 texture features each were used for a linear discriminant analysis (LDA) in combination with k nearest neighbor classification (k‐NN).
Using histology as a standard of reference, benign tumors, including subtypes, and malignant tumors were compared with regard to ADC and texture‐based values, with a one‐way analysis of variance with post‐hoc t ‐tests.
Significant differences were found in the mean ADC values between Warthin tumors and pleomorphic adenomas, as well as between Warthin tumors and benign lesions. Contrast‐enhanced T1‐weighted images contained the most relevant textural information for the discrimination between benign and malignant parotid masses, and also for the discrimination between pleomorphic adenomas and Warthin tumors. STIR images contained the least relevant texture features, particularly for the discrimination between pleomorphic adenomas and Warthin tumors.
Texture analysis proved to differentiate benign from malignant lesions, as well as pleomorphic adenomas from Warthin tumors, based on standard T 1w sequences (without and with contrast). Of all benign parotid masses, Warthin tumors had significantly lower ADC values than the other entities. Copyright © 2013 John Wiley & Sons, Ltd.
Purpose. To investigate the correlation of Apperent Diffusion Coefficient (ADC) values in invasive ductal breast carcinomas with detailed histologic features and enhancement ratios on dynamic contrast-enhanced MRI.
Methods and Materials. Dynamic MR images and diffusion-weighted images (DWIs) of invasive ductal breast carcinomas were reviewed in 25 (26 lesions) women. In each patient, DWI, T2WI, T1WI, and dynamic images were obtained. The ADC values of the 26 carcinomas were calculated with b-factors of 0 and 1000 s/mm2
using echoplanar DWI. Correlations of the ADC values were examined on dynamic MRI with enhancement ratios (early to delayed phase: E/D ratio) and detailed histologic findings for each lesion, including cellular density, the size of cancer nests, and architectural features of the stroma (broad, narrow, and delicate) between cancer nests.
Results. The mean ADC was 0.915 ± 0.151 × 10−3 mm2/sec. Cellular density was significantly correlated with ADC values (P = .0184) and E/D ratios (P = .0315). The ADC values were also significantly correlated to features of the stroma (broad to narrow, P = .0366).
Conclusion. The findings suggest that DWIs reflect the growth patterns of carcinomas, including cellular density and architectural features of the stroma, and E/D ratios may also be closely correlated to cellular density.
The purpose of this study was to compare, with histopathologic examination of the liver explant as the reference standard, diffusion-weighted MRI with contrast-enhanced subtraction MRI in the assessment of necrosis of hepatocellular carcinoma (HCC) after trans arterial chemoembolization (TACE).
The cases of 21 patients with HCC who underwent MRI after TACE were evaluated. Two independent observers calculated the apparent diffusion coefficient (ADC) of HCC and measured percentage tumor necrosis on subtraction images. The ADCs of necrotic and viable tumor tissues were compared. ADC and percentage necrosis on subtraction images were correlated with percentage necrosis found at pathologic examination. Receiver operating characteristics analysis was performed on the diagnosis of complete tumor necrosis.
Twenty-eight HCCs (mean diameter, 2.3 cm) were evaluated. There were significant differences between the ADC of viable tissue and that of necrotic tumor tissue (1.33 +/- 0.41 vs 2.04 +/- 0.38 x 10(-3) mm(2)/s, p < 0.0001). There was significant moderate correlation between ADC and the pathologic finding of percentage necrosis (r = 0.64, p < 0.001) and significant strong correlation between subtraction image and pathologic percentage necrosis (r = 0.89-0.91, depending on the phase; p < 0.001). In the diagnosis of complete tumor necrosis, ADC had an area under the curve, sensitivity, and specificity of 0.85, 75%, and 87.5% compared with 0.82-0.89, 100%, and 58.3-79.1% for subtraction imaging (p > 0.5 between ADC and subtraction imaging).
Compared with diffusion-weighted imaging, contrast-enhanced MRI with subtraction technique had more significant correlation with the histopathologic findings in the evaluation of necrosis of HCC after TACE. There was no difference, however, between the two methods in diagnosis of complete tumor necrosis.
Results of the proton magnetic resonance spectroscopy carried out on normal, benign breast disease and locally advanced breast cancer patients are presented. The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering from infiltrating ductal carcinoma are dominated by the water resonance, while the spectra of the unaffected contralateral breast tissue of these patients are mainly dominated by resonance arising from lipids which is similar to the spectra of normal breast tissue obtained from volunteers (controls, n = 16). In addition to the water and lipid peaks, in majority of the patients (approximately 80%) the water suppressed spectra showed a resonance at 3.2 ppm due to choline containing compounds (TCho) before treatment. In patients receiving neoadjuvant chemotherapy, absence/reduction in choline was observed in 89% of the patients. TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%, respectively. Observation of TCho before treatment and its disappearance (or reduction) after treatment may be a useful indicator of response of locally advanced breast cancer to neoadjuvant chemotherapy.
To evaluate the value of diffusion-weighted imaging (DWI) in distinguishing between benign and malignant breast lesions.
Fifty-two female subjects (mean age = 58 years, age range = 25-75 years) with histopathologically proven breast lesions underwent DWI of the breasts with a single-shot echo-planar imaging (EPI) sequence using large b values. The computed mean apparent diffusion coefficients (ADCs) of the breast lesions and cell density were then correlated.
The ADCs varied substantially between benign breast lesions ((1.57 +/- 0.23) x 10(-3) mm(2)/second) and malignant breast lesions ((0.97 +/- 0.20) x 10(-3) mm(2)/second). In addition, the mean ADCs of the breast lesions correlated well with tumor cellularity (P < 0.01, r = -0.542).
The ADC would be an effective parameter in distinguishing between malignant and benign breast lesions. Further, tumor cellularity has a significant influence on the ADCs obtained in both benign and malignant breast tumors.
A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T1-weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water:fat peak area ratios and water T2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water:fat ratios and water T2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water:fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment.
Differentiation between the viable and necrotic parts of a tumor is essential for accurate biopsy results and for treatment planning.
To determine the role of diffusion-weighted magnetic resonance (MR) imaging in differentiation between the viable and necrotic parts of head and neck tumors.
Thirty patients with malignant head and neck tumors underwent postcontrast MR imaging. Diffusion MR imaging was done on a 1.5T unit using multislice single-shot echo-planar imaging. Diffusion-weighted MR images were acquired with a diffusion-weighted factor b of 0, 500, and 1000 s/mm(2), and an apparent diffusion coefficient (ADC) map was reconstructed. The ADC value was measured within the enhanced and nonenhanced part of the tumor, and the mean ADC values were calculated. The ADC value was correlated with biopsy results.
The mean ADC value of a viable part of the tumor was 1.17+/-0.33 x 10(-3) mm(2)/s, and of the necrotic parts of the tumor 2.11+/-0.05 x 10(-3) mm(2)/s. The difference in the ADC value between the viable and necrotic parts of the head and neck tumors was statistically significant (P<0.001). Sensitivity, specificity, and accuracy of the ADC value were 92.9%, 93%, and 94.6%, respectively.
Creation of an ADC map is an excellent method for differentiation between the viable and necrotic parts of head and neck tumors. Thus, the ADC map can be used to select the best biopsy site and to detect tumor viability in post-treatment follow-up of patients after radiation therapy.
The purpose of this study was to evaluate the utility of diffusion‐weighted magnetic resonance imaging (MRI) with echo‐planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2‐weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2‐weighted images. The minimum ADC of the high‐grade gliomas was significantly higher than that of the low‐grade gliomas. Diffusion‐weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas. J. Magn. Reson. Imaging 1999;9:53–60 © 1999 Wiley‐Liss, Inc.
A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T1-weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water : fat peak area ratios and water T2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water : fat ratios and water T2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water : fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment.
Proton magnetic resonance spectroscopy (1H MRS) of the breast has been proposed as an adjunct to the magnetic resonance imaging (MRI) examination to improve the specificity
of distinguishing malignant breast tumors from benign breast tumors. In this review, we carry out a pooled analysis of the
clinical breast 1H MRS studies undertaken to date to determine the factors that influence the diagnostic performance of this method. In total,
five studies of breast 1H MRS from four independent centers around the world have been published to date. Altogether, 153 tumors were examined, 100
of which were confirmed histologically to be malignant and 53 of which were benign. The lesions presenting a detectable composite
choline signal in their corresponding 1H MR spectra were diagnosed as malignant, whereas the lesions with no choline signal were diagnosed as benign. The sensitivity
and specificity of breast 1H MRS for detecting breast cancer were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to 93%), respectively,
and both values could be as high as 92% after technical exclusions. In a subgroup of 20 young women, the sensitivity and the
specificity of the method approached 100%. The factors limiting the sensitivity of the examination were mainly technical.
The use of the composite choline signal as a marker for malignancy in breast 1H MRS is a robust method with highly reliable interpretation, because it is based on the appearance of a single peak. The
method is likely to provide even better results with technologic advances in breast MRS that lead to the improved detection
of the composite choline signal.
Breast cancer incidence is increasing worldwide and early detection is crucial for patient management. In vivo MR (magnetic resonance) spectroscopy (MRS) is an emerging clinical tool for noninvasive diagnosis and for assessment of tumor response to therapy. Elevated total choline (tCho)-containing compounds at 3.2 ppm seen in the in vivo proton MR spectrum of breast cancer patients have been documented as characteristic of malignancy. Methods for in vivo quantification of absolute tCho concentration have also been developed and a cut-off value for the differentiation of normal, benign, and malignant breast tissues has been reported. Association of tCho with various hormonal factors such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu has been reported, perhaps owing to the molecular heterogeneity of breast lesions. Many studies have documented that tCho can be used for assessing the tumor response to therapy. The limitations of breast MRS include low sensitivity, which makes it difficult to examine small-sized lesions. Further improvements in breast MRS protocols require developments of robust quantitative methods, improved design of coils with high-sensitivity, advanced magnetic field-shimming procedures, and better postprocessing algorithms. Studies have also shown that inclusion of MRS findings with MRI (magnetic resonance imaging) increases the specificity of diagnosis.
In vivo 1H MRS is rapidly developing as a clinical tool for diagnosing and characterizing breast cancers. Many in vivo and in vitro experiments have demonstrated that alterations in concentrations of choline-containing metabolites are associated with malignant transformation. In recent years, considerable efforts have been made to evaluate the role of 1H MRS measurements of total choline-containing compounds in the management of patients with breast cancer. Current technological developments, including the use of high-field MR scanners and quantitative spectroscopic analysis methods, promise to increase the sensitivity and accuracy of breast MRS. This article reviews the literature describing in vivo MRS in breast cancer, with an emphasis on the development of high-field MR scanning and quantitative methods. Potential applications of these technologies for diagnosing suspicious lesions and monitoring response to chemotherapy are discussed.
In this article, the author studies the mechanism of formation of necrotic cores in the growth of tumors by using rigorous analysis of a mathematical model. The model modifies a corresponding tumor growth model proposed by Byrne and Chaplain in 1996, in the case where no inhibitors exist. The modification is made such that both necrotic tumors and nonnecrotic tumors can be considered in a joint way. It is proved that if the nutrient supply is below a threshold value, then there is not dormant tumor, and all evolutionary tumors will finally vanish. If instead the nutrient supply is above this threshold value then there is a unique dormant tumor which can either be necrotic or nonnecrotic, depending on the level of the nutrient supply and the level of dead-cell dissolution rate, and all evolutionary tumors will converge to this dormant tumor. It is also proved that, in the second case, if the dormant tumor is necrotic then an evolutionary tumor will form a necrotic core at a finite time, and if the dormant tumor is nonnecrotic then an evolutionary tumor will also be nonnecrotic from a finite time.
This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion-weighted echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma-related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion-weighted images with b-values of 30 and 300 seconds/mm2 was evaluated. Hypercellular marrow (normal and lymphoma-related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757–760. © 2001 Wiley-Liss, Inc.
The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas. J. Magn. Reson. Imaging 1999;9:53–60 © 1999 Wiley-Liss, Inc.
Quantitative diffusion measurements were performed in tumors arising from inoculation of nude mice with two human breast cancer cell lines (MCF7 and T47D) to evaluate the specificity of this technique for characterizing solid tumors. ADC maps were compared to histology and correlated well with gross tumor morphology. Measured ADCs were highly specific for viable and necrotic tumor in the five T47D tumors included in this study (P < 0.02), while only two of the five MCF7 tumors studied developed distinguishable areas of necrosis. No statistically significant difference was observed in ADCs from viable tumor between the different cell lines (P > 0.05).
The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P < 0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P < 0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast (1) H magnetic resonance spectroscopy in diagnostic workup. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
MRI and in vivo MRS have rapidly evolved as sensitive tools for diagnosis and therapeutic monitoring in cancer research. In vivo MRS provides information on tumor metabolism, which is clinically valuable in the diagnosis and assessment of tumor response to therapy for the management of women with breast diseases. Several centers complement breast MRI studies with (1)H MRS to improve the specificity of diagnosis. Malignant breast tissues show elevated water-to-fat ratio and choline-containing compounds (total choline, tCho), and any effect of therapy on tissue viability or metabolism will be manifested as changes in these levels. Sequential (1)H MRS studies have shown significantly reduced tCho levels during the course of therapy in patients who were responders. However, there are challenges in using in vivo MRS because of the relatively low sensitivity in detecting the tCho resonance with decreased lesion size or significant reduction in the tumor volume during therapy. MRS is also technically challenging because of the low signal-to-noise ratio and heterogeneous distribution of fat and glandular tissues in the breast. MRS is best utilized for the diagnosis of focal masses, most commonly seen in patients with ductal-type neoplasms; however, it has limitations in detecting nonfocal masses, such as the linear pattern of tumors seen in invasive lobular carcinoma. Further work is required to assess the clinical utility of quantitative MRS, with the goal of automation, which will reduce the subjectivity currently inherent in both qualitative and semi-quantitative MRS.
Diffusion-weighted imaging provides a novel contrast mechanism in magnetic resonance (MR) imaging and has a high sensitivity in the detection of changes in the local biologic environment. A significant advantage of diffusion-weighted MR imaging over conventional contrast material-enhanced MR imaging is its high sensitivity to change in the microscopic cellular environment without the need for intravenous contrast material injection. Approaches to the assessment of diffusion-weighted breast imaging findings include assessment of these data alone and interpretation of the data in conjunction with T2-weighted imaging findings. In addition, the analysis of apparent diffusion coefficient (ADC) value can be undertaken either in isolation or in combination with diffusion-weighted and T2-weighted imaging. Most previous studies have evaluated ADC value alone; however, overlap in the ADC values of malignant and benign disease has been observed. This overlap may be partly due to selection of b value, which can influence the concomitant effect of perfusion and emphasize the contribution of multicomponent model influences. The simultaneous assessment of diffusion-weighted and T2-weighted imaging data and ADC value has the potential to improve specificity. In addition, the use of diffusion-weighted imaging in a standard breast MR imaging protocol may heighten sensitivity and thereby improve diagnostic accuracy. Standardization of diffusion-weighted imaging parameters is needed to allow comparison of multicenter studies and assessment of the clinical utility of diffusion-weighted imaging and ADC values in breast evaluation.
Cellular density is a major factor for change in the apparent diffusion coefficient (ADC). The authors hypothesized that loss of tumor cells after Gamma Knife surgery (GKS) may alter the ADC value and used diffusion weighted MR imaging (DW imaging) to evaluate cellular changes in brain tumors to detect their treatment response and the efficacy of GKS.
In this paper the authors describe a prospective trial involving 86 patients harboring 38 solid or predominantly solid brain metastases, 30 meningiomas, and 24 acoustic neuromas that were treated by GKS. The patients underwent serial MR imaging examinations, including DW imaging, before treatment and at multiple intervals following GKS. Follow-up MR images and clinical outcomes were reviewed at 3-month intervals for metastatic lesions and at 6-month intervals for benign tumors. Apparent diffusion coefficients were calculated from echo planar DW images, and mean ADC values were compared at each follow-up.
The mean ADC value for all meningiomas was 0.82 ± 0.15 × 10-3 mm2/sec before GKS. The mean ADC value as of the last mean follow-up of 42 months was 1.36 ± 0.19 × 10-3 mm2/sec, a significant increase compared to that before treatment (p < 0.0001). Calcification (p = 0.006) and tumor recurrence (p = 0.025) significantly prevented a rise in the ADC level.The mean ADC value for all solid acoustic neuromas was 1.06 ± 0.17 × 10-3 mm2/sec before GKS. The mean ADC value as of the last mean follow-up of 36 months was 1.72 ± 0.26 × 10-3 mm2/sec, a significant increase (p =0.0002) compared with values before GKS. At the last mean MR imaging follow-up there appeared to be tumor enlargement in 3 patients (12.5%); however, since the ADC values in these patients were significantly higher than the preradiosurgery values, the finding was considered to be a sign of radiation necrosis rather than tumor recurrence. The mean ADC value of metastatic tumors was 1.05 ± 0.12 × 10-3 mm2/sec before GKS. This value rose significantly(p < 0.0001) to 1.64 ± 0.18 × 10-3 mm2/sec after GKS at a mean follow-up of 9.4 months. Magnetic resonance imaging showed that 89% of these tumors had been controlled by GKS. In 2 patients there were enlarged lesions, but the ADC values were the same as pre-GKS levels, and therefore, the lesions were deemed recurrent.
Apparent diffusion coefficient values may be useful in evaluating treatment results before a definitive change in volume is evident on imaging studies. In some patients in whom imaging findings are equivocal, ADC values may also be used to distinguish radiation-induced necrosis from tumor recurrence.(DOI: 10.3171/2010.7.GKS10864)
The potential of total choline (tCho) signal-to-noise ratio (SNR) (ChoSNR) and tumor volume in the assessment of tumor response in locally advanced breast cancer (LABC) patients (n = 30) undergoing neoadjuvant chemotherapy (NACT) was investigated using magnetic resonance spectroscopic imaging (MRSI) and conventional MRI at 1.5 T. Experiments were carried out sequentially at four time-points: prior to therapy and after I, II and III NACT and ChoSNR, and the tumor volume was measured. The MR response was compared with the clinical response. Sequential data of 25 patients were retrospectively analyzed by classifying them as clinical responders and non-responders. In 14 responders, the pre-therapy ChoSNR was 7.8 +/- 5.1. In 10/14 responders, no choline was observed after III NACT while in the remaining four patients the ChoSNR was reduced to 3.6 +/- 1.1 (p < 0.05). Non-responders showed no statistically significant change in ChoSNR. After III NACT, the tumor volume reduced by 84.0 +/- 14.8% in responders. Using receiver operating curve (ROC) analysis, cut-off values of 53% for ChoSNR and 47.5% for volume were obtained to differentiate responders from non-responders. The sensitivity to detect responders from non-responders using ChoSNR was 85.7% with 91% specificity while 100% sensitivity was observed for volume but with reduced specificity of 73%. Our results indicate that ChoSNR may serve as a useful parameter to predict tumor response to NACT with higher specificity compared to volume, suggesting its potential in effective treatment management.
Abnormal vascularization of malignant tumors is associated with the development of microregions of heterogeneous cells and
environments. Experimental models such as multicell spheroids and a variety of new techniques are being used to determine
the characteristics of these microregions and to study the interactions of the cells and microenvironments. The special cellular
microecology of tumors influences responsiveness to therapeutic agents and has implications for future directions in cancer
research.
In a previous publication it was shown that the level of platelet adhesiveness in a group of patients with focal cerebral vascular disease was higher than in a group of control subjects. In the present study selected clinical factors in the patients were analysed in terms of platelet adhesiveness values.The level of platelet adhesiveness bore no relationship to the clinical category (single stroke, multiple strokes, transient vascular insufficiency), morbidity, the presence of ischaemic heart disease, the level of initial diastolic blood pressure, the age at onset of cerebral vascular disease, the duration of symptoms and the time between the last stroke and the estimation of platelet adhesiveness. In patients who also had symptoms of peripheral vascular disease, the mean platelet adhesiveness was higher than in the remaining patients.
Using the rotating glass bulb method it is shown that patients with cerebrovascular disease have platelets which are significantly more adhesive to glass than those of control subjects. Hyperadhesiveness is demonstrable within a day of cerebral infarction, and there is no evidence that it alters significantly within the first 6 weeks of infarction, or during a period of 6 months in established cerebral vascular disease. Platelet adhesiveness is independent of age and sex, as well as platelet count and the several other laboratory tests studied.Although there was no significant difference in mean platelet adhesiveness in patients and controls when stickiness was measured by the glass bead filter method, a good linear correlation was found between platelet adhesiveness values obtained by using the two methods simultaneously in 89 subjects.
Cerebral angiographic findings in ischaemic stroke are described and discussed in detail. Though the Indian patients studied had altogether different social customs, living standards, and dietary habits from Western people, the relative incidence of various cerebral vascular lesions did not differ significantly. Irrespective of the poor nutritional status of the patients, thrombosis associated with atherosclerosis was chiefly responsible for a non-embolic cerebral infarction. Atherothrombosis in the young normotensive persons not showing any evidence of arteritis, diabetes mellitus, or hypercholesterolaemia was also identified.The grave risks involved in cerebral angiography in cases of acute stroke are re-emphasized.As to prognosis, the nutritional status, the type and territory of an ictal lesion, and the blood levels of sugar and cholesterol had no significant influence on the immediate survival-after a non-embolic cerebral infarction. However, a significantly greater number of deaths were encountered in the hypertensive patients. Female patients and patients with a large cerebral infarction had a poor prognosis.
The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas.
Diffusion-weighted imaging was used to study the relationship between apparent diffusion coefficient (ADC) and cell volume fraction in cell suspensions and packed arrays. Cell volume fraction was varied by changing extracellular fluid osmolarity (for human glial cells) and by changing cell density (for human glial and red blood cells). In packed arrays of glial cells, ADC increased 10% when cells shrank and decreased 13% when cells swelled. ADC decreased 34% as cell density increased from 0 to 72%. In erythrocyte suspensions, ADC decreased 90% as the cell density increased from 0 to 89%. These results agree with theoretical predictions.
The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.
This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion-weighted echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma-related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion-weighted images with b-values of 30 and 300 seconds/mm(2) was evaluated. Hypercellular marrow (normal and lymphoma-related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757-760.
Diffusion-weighted images (DWIs) have been used to study various diseases, particularly since echo-planar techniques shorten examination time. Our hypothesis was that DWIs and tumor apparent diffusion coefficients (ADCs) could provide additional useful information in the diagnosis of patients with brain tumors.
Using a 1.5-T MR unit, we examined 56 patients with histologically verified or clinically diagnosed brain tumors (17 gliomas, 21 metastatic tumors, and 18 meningiomas). We determined ADC values and signal intensities on DWIs both in the solid portion of the tumor and in the peritumoral, hyperintense areas on T2-weighted images. We also evaluated the correlation between ADC values and tumor cellularity in both gliomas and meningiomas.
The ADCs of low-grade (grade II) astrocytomas were significantly higher (P =.0004) than those of other tumors. Among astrocytic tumors, ADCs were higher in grade II astrocytomas (1.14 +/- 0.18) than in glioblastomas (0.82 +/- 0.13). ADCs and DWIs were not useful in determining the presence of peritumoral neoplastic cell infiltration. The ADC values correlated with tumor cellularity for both astrocytic tumors (r = -.77) and meningiomas (r = -.67).
The ADC may predict the degree of malignancy of astrocytic tumors, although there is some overlap between ADCs of grade II astrocytomas and glioblastomas.
To determine if water diffusivity within lymphomas and high-grade astrocytomas correlates with cellularity.
Echo-planar diffusion-weighted magnetic resonance (MR) images obtained in 11 patients with brain lymphomas (19 lesions) and in 17 patients with astrocytomas (19 lesions) were retrospectively reviewed. Regions of interest were drawn on apparent diffusion coefficient (ADC) maps in enhancing tumor. ADC values were normalized by dividing ADC values of tumors by those of normal-appearing regions and expressing the quotient as a ratio. Histologic samples from 11 patients with astrocytomas (11 lesions) and seven patients with lymphoma (seven lesions) were reviewed. Cellularity was measured by calculating the percentage of nuclear area and the percentage of cytoplasmic area and expressing the results as the nuclear-to-cytoplasmic (N/C) ratio. The ADC and N/C ratios of both tumor types were compared by using a two-tailed t test.
Mean ADC ratio of lymphomas was 1.15 (SD, 0.33; standard error of the mean [SEM], 0.10), and that of high-grade astrocytomas was 1.68 (SD, 0.48; SEM, 0.11) (P <.01). Mean N/C ratio of lymphoma was 1.45 (SD, 0.94; SEM, 0.36), and that of high-grade astrocytomas was 0.24 (SD, 0.18; SEM, 0.05) (P <.01).
Measurements of water diffusivity and cellularity suggest that higher cellularity contributes to more restricted diffusion.
Proton magnetic resonance spectroscopy ((1)H MRS) of the breast has been proposed as an adjunct to the magnetic resonance imaging (MRI) examination to improve the specificity of distinguishing malignant breast tumors from benign breast tumors. In this review, we carry out a pooled analysis of the clinical breast (1)H MRS studies undertaken to date to determine the factors that influence the diagnostic performance of this method. In total, five studies of breast (1)H MRS from four independent centers around the world have been published to date. Altogether, 153 tumors were examined, 100 of which were confirmed histologically to be malignant and 53 of which were benign. The lesions presenting a detectable composite choline signal in their corresponding (1)H MR spectra were diagnosed as malignant, whereas the lesions with no choline signal were diagnosed as benign. The sensitivity and specificity of breast (1)H MRS for detecting breast cancer were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to 93%), respectively, and both values could be as high as 92% after technical exclusions. In a subgroup of 20 young women, the sensitivity and the specificity of the method approached 100%. The factors limiting the sensitivity of the examination were mainly technical. The use of the composite choline signal as a marker for malignancy in breast (1)H MRS is a robust method with highly reliable interpretation, because it is based on the appearance of a single peak. The method is likely to provide even better results with technologic advances in breast MRS that lead to the improved detection of the composite choline signal.
Complete pathologic response of breast carcinoma to neoadjuvant chemotherapy is a well defined outcome that correlates with prolonged survival. Categorization of incomplete response depends on accurate measurement of residual tumor size but is complicated by the variable histopathologic changes that occur within the tumor bed. In the current study, the authors investigated the contribution of assessing tumor cellularity in the pathologic evaluation of response to chemotherapy.
The slides from diagnostic core needle biopsy and the subsequent matched resection specimens were examined in 240 patients with breast carcinoma: 120 "treated" patients who received neoadjuvant chemotherapy and 120 "control" patients who received primary surgical management within a few weeks of diagnosis. Clinical response and residual tumor size were evaluated in 108 treated patients who completed a clinical trial with paclitaxel and then received combined 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Tumor cellularity was assessed from hematoxylin and eosin-stained tissue sections as the percentage of tumor area that contained invasive carcinoma.
After neoadjuvant chemotherapy, tumor cellularity decreased from a median of 40% in core needle biopsy to 10% in resection specimens (P<0.01; Wilcoxon signed rank test). The cellularity of core needle biopsy (median, 30%) tended to underestimate the cellularity of resection specimens (median, 40%) in the control group (P<0.01). Changes in cellularity varied within each clinical response category, particularly partial response and minor response. The greatest reduction was observed in the cellularity of residual primary tumors that measured < or =1 cm (pathologic T1a [pT1a] and pT1b tumors), but changes in cellularity varied in the pT1, pT2, and pT3 residual tumor categories. The shape of the distribution of tumor size, expressed as the greatest dimension in cm, was similar in the control group and the treatment group (excluding complete pathologic response); however, when residual tumor size and cellularity were combined, the distribution of pathologic response shifted left (toward complete response) with a steep decline, suggesting that many tumors had a large reduction in cellularity but little change in the tumor size.
Cellularity of the tumor mass was reduced significantly by neoadjuvant chemotherapy, and the change varied widely in different categories of clinical response. Although residual tumors measuring < or =1 cm in greatest dimension had the most reduction in tumor cellularity, there was broad variability for all residual tumor groups (pT1-pT3). The frequency distribution of residual tumor size was altered markedly by the inclusion of tumor cellularity, indicating that the product of pathologic size and tumor cellularity may provide more accurate pathologic response information than tumor size alone.
The purpose of this study was to investigate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value in differentiating benign and malignant breast lesions and evaluating the detection accuracy of the cancer extension.
We used DWI to obtain images of 191 benign and malignant lesions (24 benign, 167 malignant) before surgical excision. The ADC values of the benign and malignant lesions were compared, as were the values of noninvasive ductal carcinoma (NIDC) and invasive ductal carcinoma (IDC). We also evaluated the ADC map, which represents the distribution of ADC values, and compared it with the cancer extension.
The mean ADC value of each type of lesion was as follows: malignant lesions, 1.22+/-0.31 x 10(-3) mm2/s; benign lesions, 1.67+/-0.54 x 10(-3) mm2/s; normal tissues, 2.09+/-0.27 x 10(-3) mm2/s. The mean ADC value of the malignant lesions was statistically lower than that of the benign lesions and normal breast tissues. The ADC value of IDC was statistically lower than that of NIDC. The sensitivity of the ADC value for malignant lesions with a threshold of less than 1.6 x 10(-3) mm2/s was 95% and the specificity was 46%. A full 75% of all malignant cases exhibited a near precise distribution of low ADC values on ADC maps to describe malignant lesions. The main causes of false negative and underestimation of cancer spread were susceptibility artifact because of bleeding and tumor structure. Major histologic types of false-positive lesions were intraductal papilloma and fibrocystic diseases. Fibrocystic diseases also resulted in overestimation of cancer extension.
DWI has the potential in clinical appreciation to detect malignant breast tumors and support the evaluation of tumor extension. However, the benign proliferative change remains to be studied as it mimics the malignant phenomenon on the ADC map.
Traditionally, tumor response has been assessed via tumor size measurements during the course of a treatment. However, changes in these morphologically based measures occur relatively late in the course of a treatment. Alternative biomarkers are currently being evaluated to enable an earlier assessment of treatment to facilitate early cessation and cost savings. Diffusion-weighted imaging (DWI) has been identified by preclinical studies to be a likely alternative to tumor size measurements. In this study, 10 patients were examined prior to and after the first and second chemotherapy cycle time points. Longest diameter tumor measurements and apparent diffusion coefficients (ADCs) were recorded at each exam. An increase in the mean (normalized) ADC was noted as early as the first cycle time point. However, a reduction in the mean (normalized) longest diameter was only noted at the second cycle time point. Significant alterations from the baseline value were noted for ADC at the first (P=.005) and second cycle time points (P=.004). Longest diameter measurements only achieved a borderline significance at the second time point (P=.057). These results indicate that DWI may provide a suitable biomarker capable of providing an indication of response to treatment prior to tumor size measurements.
The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer.
Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment.
Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model.
The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.
Measurements of tumor apparent diffusion coefficient (ADC), volume and diameter in assessing the response of patients with locally advanced breast cancer (LABC) (n = 56) undergoing neoadjuvant chemotherapy (NACT) at four time periods (before treatment and after three cycles of NACT) were carried out at 1.5 T using diffusion-weighted imaging (DWI) and MRI. Ten benign tumors and 15 controls were also investigated. The MR tumor response was compared with the clinical response. Mean ADC before treatment of malignant breast tissue was significantly lower than that of controls, disease-free contralateral tissue of the patients, and benign lesions, and gradually increased during the course of NACT. Analysis of the percentage change in ADC, volume and diameter after each cycle of NACT between clinical responders and non-responders showed that the change in ADC after the first cycle was statistically significant compared with volume and diameter, indicating its potential in assessing early response. After the third cycle, the sensitivity for differentiating responders from non-responders was 89% for volume and diameter and 68% for ADC, and the respective specificities were 50%, 70% and 100%. A sensitivity of 84% (specificity of 60% with an accuracy of 76%) was achieved when all three variables were taken together to predict the response. A cut-off value of ADC was also calculated using receiver operator characteristics analysis to discriminate between normal, benign and malignant breast tissue. Similarly, a cut-off value for ADC, volume and diameter was obtained after the second and third cycles of NACT to predict tumor response. The results show that ADC is more useful for predicting early tumor response to NACT than morphological variables, suggesting its potential in effective treatment management.
To evaluate the usefulness of apparent diffusion coefficient (ADC) for the differential diagnosis of breast tumors and to determine the relation between ADC and tumor cellularity.
One hundred and thirty-six female patients (age range, 17-83 years; average age, 51.7 years) with 140 histologically proven breast tumors underwent diffusion-weighted magnetic resonance (MR) imaging (DWI) using the spin-echo echo-planar technique, and the ADCs of the tumors were calculated using 3 different b values, 0, 500, and 1000 s/mm(2). The diagnoses consisted of fibroadenoma (FA, n=16), invasive ductal carcinoma, not otherwise specified (IDC, n=117), medullary carcinoma (ME, n=3) and mucinous carcinoma (MU, n=4). Tumor cellularity was calculated from surgical specimens. The ADCs of breast tumors and cellularity were compared between different histological types by analysis of variance and Scheffe's post hoc test. The correlation between tumor cellularity and ADC was analyzed by Pearson correlation test.
Significant differences were observed in ADCs between FA and all types of cancers (P<0.05) and between MU and other types of cancers (P<0.01) and in cellularity between FA and cancers except MU (P<0.01) and between MU and other types of cancers (P<0.01). There was an inverse correlation between ADC and tumor cellularity (P<0.01, r(2)=0.451).
The ADC may potentially help in differentiating benign and malignant breast tumors. Tumor ADC correlates inversely with tumor cellularity.
Breast magnetic resonance spectro-scopy (MRS) In: Harris RK, Wasylishen RE, editors. Encyclo-pedia of magnetic resonance
- U Sharma
- Jagannathan
- Nr
Sharma U, Jagannathan NR. Breast magnetic resonance spectro-scopy (MRS). In: Harris RK, Wasylishen RE, editors. Encyclo-pedia of magnetic resonance. Chichester: John Wiley; 2009, doi: 10.1002/9780470034590.emrstm1167. Published 15th December.