Xiaobing Fan

University of Illinois at Chicago, Chicago, Illinois, United States

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Publications (72)198.17 Total impact

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    ABSTRACT: MRI methods that accurately identify various stages of mouse mammary cancer could provide new knowledge that may have a direct impact on the management of breast cancer in patients. This research investigates whether we can accurately follow the progression from in situ to invasive cancer by the evaluation of in vivo and ex vivo MRI, and in comparison with histology as the gold standard for the diagnosis and staging of cancer. Six C3(1)SV40Tag virgin female mice, aged 12–16 weeks, were studied. At this age, these mice develop in situ cancer that resembles human ductal carcinoma in situ (DCIS). Fast spin-echo images of inguinal mammary glands were acquired at 9.4 T. After in vivo MRI, mice were sacrificed; inguinal mammary glands were excised and fixed in formalin for ex vivo MRI. Three-dimensional, volume-rendered, in vivo and ex vivo MR images were then correlated with histology. High-resolution ex vivo scans facilitated the comparison of in vivo scans with histology. The sizes of mammary cancers classified as in situ on the basis of histology ranged from 150 to 400 µm in largest diameter, and the average signal intensity relative to muscle was 1.40 ± 0.18 on T2-weighted images. Cancers classified as invasive on the basis of histology were >400 µm in largest diameter, and the average intensity relative to muscle on T2-weighted images was 2.34 ± 0.26. Using a cut-off of 400 µm in largest diameter to distinguish between in situ and invasive cancers, a T2-weighted signal intensity of at least 1.4 times that of muscle for in situ cancer, and at least 2.3 times that of muscle for invasive cancer, 96% of in situ and 100% of invasive cancers were correctly identified on in vivo MRI, using histology as the gold standard. Precise MRI–histology correlation demonstrates that MRI reliably detects early in situ cancer and differentiates in situ from invasive cancers in the SV40Tag mouse model of human breast cancer. Copyright
    NMR in Biomedicine 07/2015; DOI:10.1002/nbm.3348 · 3.56 Impact Factor
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    ABSTRACT: PurposeTo develop a method for mapping the B1 field using a reference signal from a tissue with known T1.Methods Flip angle correction factors were calculated in a region with a known “gold standard” T1; by comparing T1 values from a variable flip angle (VFA) sequence to the “gold standard” and correcting the value of the Ernst angle. The resulting partial B1 map was interpolated for all other regions. In the breast, fat is an ideal reference tissue because its T1 is spatially homogeneous and interpatient variability is low. This method was tested with scans of phantoms and patients (n = 4) on a 3T magnet. The performance of the method was evaluated by comparing the results of VFA T1 mapping with and without B1 correction to inversion recovery (IR) T1 maps.ResultsPhantom data determined that a linear inverse distance weighted interpolation accurately recovered the full B1 map. Use of interpolated maps to correct the VFA data in vivo, reduced the average difference in the T1 of parenchyma between VFA and IR results from 58% to 8%.Conclusion This proof-of-principle study showed that it is possible to recover a full and accurate map of the B1 field in the breast by using a reference tissue (fat) with an accurately measured T1. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2015; DOI:10.1002/mrm.25751 · 3.40 Impact Factor
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    ABSTRACT: To compare DCE-MRI parameters from scans of breast lesions at 1.5 Tesla and 3 Tesla. Eleven patients underwent paired MRI examinations on both Philips 1.5T and 3T systems using a standard clinical fat-suppressed, T1-weighted DCE-MRI protocol, with 70-76 s temporal resolution. Signal intensity-versus-time curves were fit with an empirical mathematical model to obtain semi-quantitative measures of uptake and washout rates as well as time-to-peak enhancement (TTP). Maximum percent enhancement and signal enhancement ratio (SER) were also measured for each lesion. Percent differences between parameters measured at the two field strengths were compared. TTP and SER parameters measured at 1.5T and 3T were similar; with mean absolute differences of 19% and 22% respectively. Maximum percent signal enhancement was significantly higher at 3T than at 1.5T (p=0.006). Qualitative assessment showed that image quality was significantly higher at 3T (p=0.005). Our results suggest that TTP and SER are more robust to field strength change than other measured kinetic parameters and therefore measurements of these parameters can be more easily standardized than measurements of other parameters derived from DCE-MRI. Semi-quantitative measures of overall kinetic curve shape showed higher reproducibility than discrete classification of kinetic curve early and delayed phases in a majority of the cases studied. Advances in knowledge: Qualitative measures of curve shape are not consistent across field strength even when acquisition parameters are standardized. Quantitative measures of overall kinetic curve shape, in contrast, have higher reproducibility.
    The British journal of radiology 03/2015; 88(1049):20150021. DOI:10.1259/bjr.20150021 · 2.02 Impact Factor
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    ABSTRACT: IntroductionPrevious work from this laboratory demonstrated that magnetic resonance imaging (MRI) detects early murine mammary cancers and reliably differentiates between in situ and invasive cancer. Based on this previous work, we used MRI to study initiation and progression of murine mammary cancer, and monitor the transition from the in situ to the invasive phase.Methods In total, seven female C3(1) SV40 Tag mice were imaged every two weeks between the ages of 8 to 23 weeks. Lesions were identified on T2-weighted images acquired at 9.4 Tesla based on their morphology and growth rates. Lesions were traced manually on MR images of each slice. Volume of each lesion was calculated by adding measurements from individual slices. Plots of lesion volume versus time were analyzed to obtain the specific growth rate (SGR). The time at which in situ cancers (referred to as `mammary intraepithelial neoplasia (MIN)¿) and invasive cancers were first detected; and the time at which in situ cancers became invasive were recorded.ResultsA total of 121 cancers (14 to 25 per mouse) were identified in seven mice. On average the MIN lesions and invasive cancers were first detected when mice were 13 and 18 weeks old, respectively. The average SGR was 0.47¿±¿0.18 week-1 and there were no differences (P >0.05) between mice. 74 lesions had significantly different tumor growth rates before and after ~17 weeks of age; with average doubling times (DT) of 1.88 and 1.27 weeks, respectively. The average DT was significantly shorter (P <0.0001) after 17 weeks of age. However, the DT for some cancers was longer after 17 weeks of age, and about 10% of the cancers detected did not progress to the invasive stage.ConclusionsA wide range of growth rates were observed in SV40 mammary cancers. Most cancers transitioned to a more aggressive phenotype at approximately 17 weeks of age, but some cancers became less aggressive. The results suggest that the biology of mammary cancers is extremely heterogeneous. This work is a first step towards use of MRI to improve understanding of factors that control and/or signal the development of aggressive breast cancer.
    Breast cancer research: BCR 12/2014; 16(6):495. DOI:10.1186/s13058-014-0495-6 · 5.88 Impact Factor
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    ABSTRACT: This pilot study compared the detectability of internal thermal marks produced with MRI-guided focused ultrasound (MRgFUS) on MRI, computed tomography (CT), ultrasonography (US), and color images from digital scanning. Internal marks made using MRgFUS could potentially guide surgical, biopsy or radiotherapy procedures. New Zealand White rabbits (n = 6) thigh muscle were marked using a Philips MRgFUS system. Before and after sonications, rabbits were imaged using T1- and T2-weighted MRI. Then rabbits were sacrificed and imaging was performed using CT and US. After surgical excision specimens were scanned for color conspicuity analysis. Images were read by a radiologist and quantitative analysis of signal intensity was calculated for marks and normal muscle. Of a total of 19 excised marks, approximately 79%, 63%, and 62% were visible on MRI, CT, and US, respectively. The average maximum temperature elevation in the marks during MRgFUS was 39.7 ± 10.1 °C, and average dose diameter (i.e., the diameter of the area that achieved a thermal dose greater than 240 cumulative equivalent minutes at 43 °C) of the mark at the focal plane was 7.3 ± 2.1 mm. On MRI the average normalized signal intensities were significantly higher in marks compared to normal muscle (p < 0.05). On CT, the marked regions were approximately 10 HU lower than normal muscle (p < 0.05). The results demonstrate that MRgFUS can be used to create internal marks that are visible on MRI, CT and US.
    Physica Medica 12/2014; 30(8). DOI:10.1016/j.ejmp.2014.04.007 · 1.85 Impact Factor
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    ABSTRACT: The purpose of this study was to use high resolution 3D MRI to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12–20 weeks (n = 12), were used in this study. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple. Approximately 20–25uL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4 T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p < 0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p < 0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers.
    Magnetic Resonance Imaging 08/2014; 33(1). DOI:10.1016/j.mri.2014.08.035 · 2.02 Impact Factor
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    ABSTRACT: The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is demonstrated to be capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd3+ contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, it is demonstrated that TAT-Au NPs are capable of delivering Gd3+ chelates for enhanced brain tumor imaging with a prolonged retention time of Gd3+ when compared to the free Gd3+ chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.
    Small 08/2014; 10(24). DOI:10.1002/smll.201400654 · 8.37 Impact Factor
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    ABSTRACT: Neonatal necrotizing enterocolitis (NEC) is a poorly understood life-threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam-fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4-T scanner to obtain high-resolution anatomical MR images using both gradient echo and spin echo sequences, pixel-by-pixel T2 maps using a multi-slice-multi-echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T2 measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion-weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10(-3) mm(2) /s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10(-3) mm(2) /s] and nonstressed control pups [(1.10 ± 0.06) × 10(-3) mm(2) /s]. Both T2 and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
    NMR in Biomedicine 03/2014; 27(3). DOI:10.1002/nbm.3060 · 3.56 Impact Factor
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    ABSTRACT: PURPOSE Colon cancer is a leading cause of cancer-deaths in the US. Ulcerative colitis is causally linked to colitis-associated neoplastic progression but is difficult to detect and monitor non-invasively. Goals of this study were to determine MRI characteristics of early colitis-associated colon cancer and to assess vitamin D chemopreventive efficacy. METHOD AND MATERIALS This study included CF1 female control mice (n=12), and mice treated with azoxymethane i.p. and dextran sulfate sodium in the drinking water (n=25) to induce colitis and colon cancer. Mice were fed a Western diet or Western diet supplemented with vitamin D (500 µg/kg chow). Western diets are relatively deficient in vitamin D and calcium. Mice were studied serially using anatomic and dynamic contrast enhanced MRI (DCEMRI) with a Gd-based contrast agent. In vivo MR and ex vivo histological images were co-registered using an agar based color-coded phantom in a flexible tube (2 mm o. d.) that was inserted via the rectum to the cecum. The phantom provided visual and MRI-detectable reference markers to co-register in vivo and ex vivo images. RESULTS We demonstrated that: 1) a visible reference marker could be used to successfully co-register MRI abnormalities with histological features identified in H&E stained sections; 2) T2 values distinguished normal colon from colitis, and from focal neoplastic lesions (p<0.005); 3) Ktrans values assessed by DCEMRI (a measure of perfusion/capillary permeability) reliably distinguished normal colon from tumor (0.12±0.01 min-1 vs. 0.61±0.05 min-1, respectively, p<0.001); 4) blood vessel diameters were >3-fold larger adjacent to early colonic tumors compared to vessels in control mice, suggesting that MRI might be used to detect dilated blood vessels as biomarkers of early colorectal cancer; 5) Vitamin D reduced the number of colonic tumors and degree of inflammation detected by MRI (p<0.001). CONCLUSION A novel technique was successfully developed to co-register MR and histological images. Several reliable image-based markers for colitis and colon cancer were identified. These MRI methods could monitor the chemopreventive efficacy of vitamin D in this model in real time and without sacrifice. CLINICAL RELEVANCE/APPLICATION Non-invasive MRI/DCEMRI studies of colitis and colon cancer in mice will improve understanding of these diseases, produce new MRI markers to improve diagnosis, and guide development of new therapies.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: Oncolytic adenoviral virotherapy (OV) is a highly promising approach for the treatment of glioblastoma multiforme (GBM). In practice, however, the approach is limited by poor viral distribution and spread throughout the tumor mass. To enhance viral delivery, replication, and spread, we used a US Food and Drug Administration-approved neural stem cell line (NSC), HB1.F3.CD, which is currently employed in human clinical trials. HB1.F3.CD cells were loaded with an oncolytic adenovirus, CRAd-Survivin-pk7, and mice bearing various human-derived GBMs were assessed with regard to NSC migration, viral replication, and therapeutic efficacy. Survival curves were evaluated with Kaplan-Meier methods. All statistical tests were two-sided. Antiglioma activity of OV-loaded HB1.F3.CD cells was effective against clinically relevant human-derived glioma models as well as a glioma stem cell-enriched xenograft model. Median survival was prolonged by 34% to 50% compared with mice treated with OV alone (GBM43FL model median survival = 19.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.26, 95% confidence interval [CI] = 1.21 to 12.23, P = .02; GBM12 model median survival = 43.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.53, 95% CI = 1.21 to 10.38, P = .02). OV-loaded HB1.F3.CD cells were shown to effectively migrate to the contralateral hemisphere and hand off the therapeutic payload of OV to targeted glioma cells. In vivo distribution and migratory kinetics of the OV-loaded HB1.F3.CD cells were successfully monitored in real time by magnetic resonance imaging. OV-loaded NSCs retained their differentiation fate and were nontumorigenic in vivo. HB1.F3.CD NSCs loaded with CRAd-Survivin-pk7 overcome major limitations of OV in vivo and warrant translation in a phase I human clinical trial for patients with GBM.
    CancerSpectrum Knowledge Environment 07/2013; 105(13):968-977. DOI:10.1093/jnci/djt141 · 15.16 Impact Factor
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    ABSTRACT: Autoimmune ablation of pancreatic β-cells and alteration of its microvasculature may be a predictor of Type I diabetes development. A dynamic manganese-enhanced MRI (MEMRI) approach and an empirical mathematical model were developed to monitor whole pancreatic β-cell function and vasculature modifications in mice. Normal and streptozotocin-induced diabetic FVB/N mice were imaged on a 9.4T MRI system using a 3D magnetization prepared rapid acquisition gradient echo pulse sequence to characterize low dose manganese kinetics in the pancreas head, body and tail. Average signal enhancement in the pancreas (head, body, and tail) as a function of time was fit by a novel empirical mathematical model characterizing contrast uptake/washout rates and yielding parameters describing peak signal, initial slope, and initial area under the curve. Signal enhancement from glucose-induced manganese uptake was fit by a linear function. The results demonstrated that the diabetic pancreatic tail had a significantly lower contrast uptake rate, smaller initial slope/initial area under the curve, and a smaller rate of Mn uptake following glucose activation (p<0.05) compared to the normal pancreatic tail. These observations parallel known patterns of β-cell loss and alteration in supportive vasculature associated with diabetes. Dynamic MEMRI is a promising technique for assessing β-cell functionality and vascular perfusion with potential applications for monitoring diabetes progression and/or therapy.
    Magnetic Resonance Imaging 10/2012; 31(4). DOI:10.1016/j.mri.2012.09.003 · 2.02 Impact Factor
  • NMR in Biomedicine 07/2012; DOI:10.1002/nbm.2838 · 3.56 Impact Factor
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    ABSTRACT: This pilot study investigated the feasibility of using MRI based on BOLD (blood-oxygen-level-dependent) contrast to detect physiological effects of locally induced hyperthermia in a rodent tumor model. Nude mice bearing AT6.1 rodent prostate tumors inoculated in the hind leg were imaged using a 9.4 T scanner using a multi-gradient echo pulse sequence to acquire high spectral and spatial resolution (HiSS) data. Temperature increases of approximately 6 °C were produced in tumor tissue using fiber-optic-guided light from a 250 W halogen lamp. HiSS data were acquired over three slices through the tumor and leg both prior to and during heating. Water spectra were produced from these datasets for each voxel at each time point. Time-dependent changes in water resonance peak width were measured during 15 min of localized tumor heating. The results demonstrated that hyperthermia produced both significant increases and decreases in water resonance peak width. Average decreases in peak width were significantly larger in the tumor rim than in normal muscle (p = 0.04). The effect of hyperthermia in tumor was spatially heterogeneous, i.e. the standard deviation of the change in peak width was significantly larger in the tumor rim than in normal muscle (p = 0.005). Therefore, mild hyperthermia produces spatially heterogeneous changes in water peak width in both tumor and muscle. This may reflect heterogeneous effects of hyperthermia on local oxygenation. The peak width changes in tumor and muscle were significantly different, perhaps due to abnormal tumor vasculature and metabolism. Response to hyperthermia measured by MRI may be useful for identifying and/or characterizing suspicious lesions as well as guiding the development of new hyperthermia protocols.
    Physics in Medicine and Biology 04/2012; 57(9):2653-66. DOI:10.1088/0031-9155/57/9/2653 · 2.92 Impact Factor
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    ABSTRACT: This study investigates the feasibility of T(2)∗ to be a diagnostic indicator of early breast cancer in a mouse model. T(2)∗ is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. The C3(1)SV40Tag mouse model of breast cancer (n = 11) and normal FVB∕N mice (n = 6) were used to measure T(2)∗ of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T(2)∗ of water and fat signals. The measured T(2)∗ values of tumor and muscle are similar (∼15 ms), and almost twice that of lymph nodes (∼8 ms). There was a statistically significant difference (p < 0.03) between T(2)∗ in normal mammary tissue (13.7 ± 2.9 ms) and intraductal cancers (11 ± 2.0 ms) when a fat suppression pulse was applied. These are the first reported T(2)∗ measurements from single mammary ducts. The results demonstrated that T(2)∗ measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T(2)∗ for diagnostic imaging of early breast cancer.
    Medical Physics 03/2012; 39(3):1309-13. DOI:10.1118/1.3684950 · 3.01 Impact Factor
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    ABSTRACT: The purpose of this research is to evaluate the potential for identifying malignant breast lesions and their margins on large specimen MRI, in comparison to specimen radiography and clinical dynamic contrast enhanced MRI (DCE-MRI). Breast specimens were imaged with an MR scanner immediately after surgery, with an IRB-approved protocol and with the patients' informed consent. Specimen sizes were at least 5 cm in diameter and approximately 1 to 4 cm thick. Coronal and axial gradient echo MR images without fat suppression were acquired over the whole specimens using a 9.4T animal scanner. Findings on specimen MRI were compared with findings on specimen radiograph, and their volumes were compared with measurements obtained from clinical DCE-MRI. The results showed that invasive ductal carcinoma (IDC) lesions were easily identified using MRI and the margins were clearly distinguishable from nearby tissue. However, ductal carcinoma in situ (DCIS) lesions were not clearly discernible and were diffused with poorly defined margins on MRI. Calcifications associated with DCIS were visualized in all specimens on specimen radiograph. There is a strong correlation between the maximum diameter of lesions as measured by radiograph and MRI (r = 0.93), as well as the maximum diameter measured by pathology and radiograph/MRI (r>0.75). The volumes of IDC measured on specimen MRI were slightly smaller than those measured on DCE-MRI. Imaging of excised human breast lumpectomy specimens with high magnetic field MRI provides promising results for improvements in lesion identification and margin localization for IDC. However, there are technical challenges in visualization of DCIS lesions. Improvements in specimen imaging are important, as they will provide additional information to standard radiographic analysis.
    Journal of Applied Clinical Medical Physics 01/2012; 13(6):3802. · 1.11 Impact Factor
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    ABSTRACT: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a noninvasive image-guided technique used to thermally ablate solid tumors. During treatment, ultrasound reflections from distal media interfaces can shift prescribed treatment locations. The purpose of this study was to investigate the effect of normal incidence reflections from air, acrylic (modeling bone), and rubber on treatment location, temperature elevation, and heating patterns by performing ultrasound exposures in a tissue-mimicking phantom and in ex vivo porcine tissue using a clinical MR-HIFU platform. The results demonstrated a shift in treatment location toward the distal interface when targeted closer than 2 cm from the interface, especially for acrylic. Our study demonstrated that the ultrasound wave reflections from a distal air interface had less effect than the acrylic interface (modeling bone) on the heating pattern and focal location. This study provides useful information to better understand the limitations and safety concerns of performing MR-HIFU treatments with commercial clinical equipment.
    Journal of Applied Clinical Medical Physics 01/2012; 13(2):3739. · 1.11 Impact Factor
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    ABSTRACT: PURPOSE To evaluate the visibility of breast tumors on large specimen MRI, in comparison to specimen radiography and clinical dynamic contrast enhanced MRI (DCE-MRI). METHOD AND MATERIALS Breast specimens (n=15) were imaged with a MR scanner immediately after surgery, with an IRB approved protocol and with the patient’s informed consent. Specimen sizes were at least 5 cm in diameter and about 1 to 4 cm thick. Coronal and axial gradient echo MRI with and/or without fat suppression were acquired over the whole specimen using a 9.4T animal scanner with 72 mm birdcage volume coil. The lesions detected on MRI were compared with specimen radiograph and their volumes were compared with measurements obtained from clinical DCE-MRI. RESULTS Invasive ductal carcinoma (IDC) lesions were easily identified using MRI and the margins were clearly distinguishable from adjacent tissue. However, ductal carcinoma in situ (DCIS) lesions were not clearly discernible and were diffused with poorly defined margins on MRI. All calcifications associated with DCIS were visualized on specimen radiograph. The calcifications are only visible on MRI when the DCIS component is surrounded by an IDC lesion. The volumes of IDC measured on specimen MRI were not significantly different from those measured on DCE-MRI. CONCLUSION Imaging of excised human breast lumpectomy specimens with high magnetic field MRI provides promising results for improvements in lesion identification and margin localization for IDC. However, there is a technical challenge in visualization of DCIS lesions. Further improvement is necessary in visualization of DCIS lesions in order to aid pathologists in routine assessment of specimens, thus contributing to better treatment of breast cancer patients. CLINICAL RELEVANCE/APPLICATION High magnetic field specimen MRI provides better visualization of IDC lesions than radiography. Protocols and techniques developed in this study could be used to aid pathologists in routine analysis.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 12/2011
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    ABSTRACT: PURPOSE To monitor and evaluate pancreatic β-cell activity in the normal and diabetic pancreas using manganese enhanced MRI (MEMRI). METHOD AND MATERIALS Five normal and six diabetic adult Lewis rats were imaged on a 9.4T scanner. Diabetes was induced by streptozotocin treatment (60mg/kg body wt). Mn enhanced axial imaging was acquired on 16 slices through the pancreas using a Magnetization Prepared Rapid Acquisition Gradient Echo pulse sequence pre-contrast and during an IV Mn bolus (3.4g/kg body wt) and an IP glucose bolus (0.75g/kg body wt) at ~30 and ~60 min, respectively. Pancreatic regions of interest (ROIs) were drawn and average signal intensities were calculated. Then, the signal enhancement due to Mn (ΔSm = (Sm-Spre)/Spre) and glucose ( ΔSg = (Sg-Sm)/Spre) were calculated, where Spre, Sm, Sg are pre-contrast, post-Mn, and post-glucose signals, respectively. Finally, a weighted average of the signal enhancement in a volumetric ROI was calculated for each rat. In addition, serum insulin and tissue Mn concentration were measured via ELISA and atomic absorption, respectively. RESULTS Post-Mn relative signal enhancement in diabetic rats (2.7±1.2) was significantly lower than normal rats (5.6±1.5) (p<0.005). Similar results were observed in normal versus diabetic rats (0.93±0.44 vs 0.16±0.43) post-glucose administration (p<0.02). Atomic absorption data revealed that Mn concentrations in the body and tail of pancreas were ~2x greater post-glucose than baseline. Insulin concentration was significantly increased following glucose administration in normal but not in diabetic animals. CONCLUSION Elevated MEMRI contrast in the normal pancreas compared to the diabetic was supported by increased Mn content via atomic absorption. β-cell functionality was not affected by Mn as measured by glucose responsive insulin levels. MRI monitoring of β-cell mass and function is likely to detect a therapeutic window resulting in efficient pharmaceutical response and clinical benefit. CLINICAL RELEVANCE/APPLICATION Functional imaging of the pancreas would be instrumental in the development of novel therapies aimed at maintaining or increasing pancreatic function.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: PURPOSE To use an MR-guided FUS system to create internal fiducial tattoo marks that are detectable visually and by MRI, CT, and ultrasound using a live rabbit model. METHOD AND MATERIALS New Zealand rabbits were anesthetized, their hind limb placed in a degassed water bath. An integrated MRgFUS platform (Sonalleve 1.5T, Philips Healthcare) was used for sonications and MR guidance. Images were acquired using a 3D T2-w Turbo spin echo sequence (TR/TE =1000/130 msec, voxel size=1.2 mm). Dynamic temperature monitoring was performed using 2D fast field echo EPI (slice thickness 7mm, in plane resolution 1.25mm, temporal resolution 2.9 s). A variety of ultrasound powers (50-140 W), durations (5-120 sec), delays (time between sonications varies from 15-90 sec) and combinations were tested. After sonication, rabbits were sacrificed and imaging was performed using a Siemens 15L8w-S ultrasound and Philips Brilliance Big Bore CT. Surgical excision of the lesions was performed and documented photographically. RESULTS Using a combination of pulsed and continuous wave focused ultrasound, internal marks were created that could be detected on MRI, US, CT and with visual inspection at the time of surgical excision. MRI shows distinct and isolated tattoo marks generally presenting as a contiguous oval involving multiple muscle bundles. US shows a focal ovoid area of increased echogeneity that suggests focal hemorrhage. CT shows an abnormal oval structure in the rabbit thigh muscles that is consistent with marks detected by US. Visual inspection allows clear recognition of white and red tissue changes. CONCLUSION We have developed a method for marking in vivo animal muscle tissues. MRgFUS-generated tattoos are conspicuous on clinical ultrasound, CT and MRI. These marks or internal tattoos can guide surgical procedures. They can also provide fiducials for deformable registration of on-board cone-beam CT to planning images and can assist in treatment planning and real-time adjustments during radiotherapy. CLINICAL RELEVANCE/APPLICATION Successful development of a conspicuous FUS tattoo will provide new internal landmarks to guide surgeons and radiation oncologists.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: To evaluate feasibility of high-resolution, high-field ex vivo prostate magnetic resonance imaging (MRI) as an aid to guide pathologists' examination and develop in vivo MRI methods. Unfixed excised prostatectomy specimens (n = 9) were obtained and imaged immediately after radical prostatectomy under an Institutional Review Board-approved protocol. High-resolution T2-weighted (T2W) MRI of specimens were acquired with a Bruker 9.4 T scanner to correlate with whole-mount histology. Additionally, T2 and apparent diffusion coefficient (ADC) maps were generated. By visual inspection of the nine prostate specimens imaged, high-resolution T2W MRI showed improved anatomical detail compared to published low-resolution images acquired at 4 T as published by other investigators. Benign prostatic hyperplasia, adenocarcinomas, curvilinear duct architecture distortion due to adenocarcinomas, and normal radial duct distribution were readily identified. T2 was ≈10 msec longer (P < 0.03) and the ADC was ≈1.4 times larger (P < 0.002) in the normal peripheral zone compared to the peripheral zone with prostate cancer. Differences in T2 and ADC between benign and malignant tissue are consistent with in vivo data. High-resolution, high-field MRI has the potential to improve the detection and identification of prostate structures. The protocols and techniques developed in this study could augment routine pathological analysis of surgical specimens and guide treatment of prostate cancer patients.
    Journal of Magnetic Resonance Imaging 10/2011; 34(4):956-61. DOI:10.1002/jmri.22745 · 2.79 Impact Factor