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ABSTRACT: Fucosidosis is a rare lysosomal storage disorder that results in the deposition of the sugar fucose within various organs, including the central nervous system. Neuroimaging abnormalities on MR, specifically T2 shortening in the basal ganglia, have been reported as suggestive of fucosidosis. A more recent report of MR spectroscopy (MRS) of one patient provided evidence that MRS is specific for fucosidosis. We present another confirmed case with nearly identical MR spectroscopic findings along with in vitro data that support the contention that MR spectroscopy, in the setting of typical clinical and imaging features, is characteristic for this rare disorder.
Pediatric Radiology 03/2010; 40(8):1446-9. · 1.67 Impact Factor
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Harish Poptani
Academic radiology 01/2010; 17(1):1-2. · 2.09 Impact Factor
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ABSTRACT: A genetic deficiency of lysosomal alpha-mannosidase causes the lysosomal storage disease alpha-mannosidosis (AMD), in which oligosaccharide accumulation occurs in neurons and glia. The purpose of this study was to evaluate the role of magnetic resonance spectroscopy (MRS) in detecting the oligosaccharide accumulation in AMD. Five cats with AMD and eight age-matched normal cats underwent in vivo MRS studies with a single voxel short echo time (20 ms) STEAM spectroscopy sequence on a 4.7T magnet. Two voxels were studied in each cat, from the cerebellar vermis and the occipital cortex. Metabolites of brain samples from these regions were extracted with perchloric acid and analyzed by high resolution NMR spectroscopy. A significantly elevated unresolved resonance signal between 3.4 and 4. ppm was observed in the cerebellar vermis and occipital cortex of all AMD cats, which was absent in normal cats. This resonance was shown to be from carbohydrate moieties by high resolution NMR of tissue extracts. Resonances from the Glc-NAc group (1.8-2.2 ppm) along with anomeric proton signals (4.6-5.4 ppm) from undigested oligosaccharides were also observed in the extract spectra from AMD cats. This MRS spectral pattern may be a useful biomarker for AMD diagnosis as well as for assessing responses to therapy.
NMR in Biomedicine 09/2009; 23(1):74-9. · 3.21 Impact Factor
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ABSTRACT: Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease of the frontal and temporal neocortex. The single most common pathology underlying FTLD is neuronal degeneration with ubiquitin-positive but tau-negative inclusions consisting of Tar DNA binding proteins (TDP-43). Inclusions containing TDP-43 in neurons are also the most common pathology underlying motor neuron disease (MND). The present study tested the hypothesis that abnormal metabolite patterns within the dorsolateral prefrontal cortex (DLPFC) as well as the motor cortex (MC) may be observed in FTLD patients without motor disorders, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six FTLD patients with cognitive damage and ten controls underwent multivoxel (1)H MRS. Absolute concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were measured from the DLPFC, the MC and the parietal cortex (PC, an internal control). Statistical analyses were performed for group differences between FTLD patients and controls. Comparisons were also made across brain regions (PC and DLPFC; PC and MC) within FTLD patients. Significant reductions in NAA and Cr along with increased Cho and mI were observed in the DLPFC of FTLD patients compared to controls. Significantly lower NAA and higher Cho were also observed in the MCs of patients as compared to controls. Within the FTLD patients, both the MC and the DLPFC exhibited significantly decreased NAA and elevated Cho compared to the PC. However, only the DLPFC had significantly lower Cr and higher mI. Abnormal metabolite pattern from the MC supports the hypothesis that FTLD and MND may be closely linked.
Journal of Neurology 09/2009; 257(1):114-21. · 3.47 Impact Factor
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ABSTRACT: This article reviews the utility of diffusion-weighted imaging (DWI) in the diagnosis, prognosis and monitoring of treatment response in tumors arising in the head and neck region. The apparent diffusion coefficient (ADC) value, determined from DWI, can help in cancer staging and detection of subcentimeter nodal metastasis. The ADC value also discriminates carcinomas from lymphomas, benign lesions from malignant tumors and tumor necrosis from abscesses. Low pretreatment ADC values typically predict a favorable response to chemoradiation therapy. These promising reports indicate the potential of DWI as a potential biomarker for diagnosis and monitoring of treatment response in head and neck cancers. In view of the overlapping ADC values between different salivary gland tumors, care should be taken when interpreting these results and other imaging parameters should be considered for a better diagnosis. Susceptibility and motion-induced artifacts may sometimes degrade DWI image quality; however, novel techniques are being developed to overcome these drawbacks.
Future Oncology 09/2009; 5(7):959-75. · 3.16 Impact Factor
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ABSTRACT: Lactate is an important metabolite in normal and malignant tissues detectable by NMR spectroscopy; however, it has been difficult to clinically detect the lactate methyl resonance because it is obscured by lipid resonances. The selective homonuclear multiple quantum coherence transfer technique offers a method for distinguishing lipid and lactate resonances. We implemented a three-dimensional selective homonuclear multiple quantum coherence transfer version with Hadamard slice selection and two-dimensional phase encoding (Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging) on a conventional clinical MR scanner. Hadamard slice selection is explained and demonstrated in vivo. This is followed by 1-cm(3) resolution lactate imaging with detection to 5-mM concentration in 20 min on a 3-T clinical scanner. An analysis of QSel gradient duration and amplitude effects on lactate and lipid signal is presented. To demonstrate clinical feasibility, a 5-min lactate scan of a patient with a non-Hodgkin's lymphoma in the superficial thigh is reported. The elevated lactate signal coincides with the T(2)-weighted image of this tumor. As a test of selective homonuclear multiple quantum coherence transfer sensitivity, a thigh tourniquet was applied to a normal volunteer and an increase in lactate was detected immediately after tourniquet flow constriction. In conclusion, the Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging sequence is demonstrated on a phantom and in two lipid-rich, clinically relevant, in vivo conditions.
Magnetic Resonance in Medicine 09/2009; 62(6):1404-13. · 2.96 Impact Factor
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ABSTRACT: Phosphorous magnetic resonance spectroscopy ((31)P MRS) has been used to evaluate and predict treatment response in squamous cell carcinoma of the head and neck (HNSCC). Several studies have also shown the potential of proton MRS ((1)H MRS) in assessing response in HNSCC. In view of the inherent limitations associated with performing (31)P MRS in clinical settings, the current study was performed to explore whether (1)H MRS could provide similar or complementary metabolic information in HNSCC.
Fifteen patients with HNSCC underwent pretreatment magnetic resonance imaging. Both (1)H MRS and (31)P MRS were performed on viable solid parts of the metastatic lymph nodes of these patients. Peak areas of total choline (tCho) and unsuppressed water as observed on (1)H MRS and phosphomonoester (PME) and beta-nucleotide triphosphate (beta-NTP) on (31)P MRS were computed. Pearson's correlation coefficient was used to correlate the tCho/water and PME/beta-NTP ratios.
In all patients, the metastatic nodes appeared hyperintense on T2-weighted images and hypointense on T1-weighted images with variable signal intensity. A prominent resonance of tCho on (1)H MRS and a resonance of PME on (31)P MRS from the metastatic nodes of all patients were observed. A moderate correlation of 0.31 was observed between tCho/water and PME/beta-NTP (P > .05).
The biochemical pathways involved in (1)H MRS of tCho may be different from the phospholipid metabolites seen on (31)P MRS of head and neck cancers, and thus the two MRS techniques may be complementary to each other.
Academic radiology 07/2009; 16(11):1366-72. · 2.09 Impact Factor
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Gurpreet S Kapoor,
Timothy A Gocke,
Sanjeev Chawla,
Robert G Whitmore,
Ali Nabavizadeh,
Jaroslaw Krejza,
Joanna Lopinto,
Justin Plaum,
Eileen Maloney-Wilensky, Harish Poptani,
Elias R Melhem,
Kevin D Judy,
Donald M O'Rourke
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ABSTRACT: 1p19q LOH has been shown to predict radio- and chemosensitivity and prolonged survival in oligodendrogliomas (OLs). We have recently shown that magnetic resonance perfusion-weighted imaging (MR-PWI) may be useful in predicting the histopathological grade or cytogenetic type of oligodendroglial neoplasms. MR-PWI allows noninvasive determination of relative tumor blood volume (rTBV), which may reflect the degree of neoplastic angiogenesis and metabolism. The present study was aimed to correlate rTBV to the angiogenic markers and EGFR expression in oligodendroglial tumors with 1p/19q LOH or 1p LOH (Group 1) and 1p19q intact alleles or 19q LOH (Group 2), respectively. In WHO grade II neoplasms, Group 1 showed significantly greater rTBV than Group 2 (P = 0.013). However, the differences between Group 1 and Group 2 were not significant in grade III tumors. Probe-based real-time RT-PCR analyses showed that 12% of Group 2 high-grade tumors with intact 1p19q exhibited dramatic EGFR overexpression (designated EGFR-high). Grade III neoplasms showed a significantly higher rTBV than grade II neoplasms. Group 1 tumors showed significantly higher rTBV than Group 2 tumors, independent of the EGFR-high subtype. Real-time RT-PCR analyses showed increased expression of VEGF, CD31 and CD105 in Group 1 tumors as compared to Group 2 tumors, excluding the EGFR-high subtype. Multivariable linear regression analysis showed a significant association of rTBV with 1p19q LOH, and expression of EGFR and VEGF. Therefore, the combined use of extensive molecular profiling and advanced MR imaging modalities may improve the accuracy of tumor grading, provide prognostic information, and has the potential to influence treatment decisions.
Journal of Neuro-Oncology 06/2009; 92(3):373-86. · 3.21 Impact Factor
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ABSTRACT: The study of vascular targeted cancer therapies is critically dependent on the development of noninvasive methods for assessing changes in vascular permeability and blood flow in small-animal tumor models.
A multicoil apparatus consisting of two receive-only surface coils for observation of the rat brain and chest, a whole-body transmit-only volume coil, and the switching circuitry necessary for sharing a single receiver channel between the two surface coils was constructed for the parallel observation of left ventricular arterial input function and magnetic resonance imaging (MRI) signal intensity kinetics in the rat brain. Dynamic contrast-enhanced MRI was performed on four Fischer rats bearing intracranial 9L gliomas, and the dynamic data were evaluated using the bolus-enhanced relaxation overview (BOLERO) model yielding maps of K(trans), v(e), and tau(i) values from the tumor.
The use of the multicoil apparatus resulted in images with high signal-to-noise ratios from the rat brain and chest in parallel, with no detectable crosstalk between the surface coils. The BOLERO method accurately fit the observed data to within experimental error. Mean values of the parameters generated by the BOLERO analysis for the tumor were K(trans) = 0.023 +/- 0.014 s(-1), tau(i) = 1.3 +/- 0.6 seconds, and v(e) = 0.51. K(trans) and tau(i) values were slightly elevated in the tumor periphery, whereas v(e) was elevated in the tumor core.
These results demonstrate the feasibility of measuring quantitative dynamic contrast-enhanced MRI parameters in a rat brain tumor model using a multicoil apparatus. These methods might play an important role in determining the efficacy of antiangiogenic therapies in small-animal models.
Academic radiology 04/2009; 16(3):341-50. · 2.09 Impact Factor
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ABSTRACT: The aim of this study was to investigate the utility of apparent diffusion coefficient (ADC) for prediction and early detection of treatment response in head and neck squamous cell carcinomas (HNSCC).
Diffusion-weighted magnetic resonance imaging studies were performed on 40 patients with newly diagnosed HNSCC before, during, and after the end of chemoradiation therapy. Analysis was done on data from 33 patients after exclusion of 7 patients that had incomplete data.
Pretreatment ADC value of complete responders (1.04 +/- 0.19 x 10(-3) mm2/s) was significantly lower (P < 0.05) than that from partial responders (1.35 +/- 0.30 x 10(-3) mm2/s). A significant increase in ADC was observed in complete responders within 1 week of treatment (P < 0.01), which remained high until the end of the treatment. The complete responders also showed significantly higher increase in ADC than the partial responders by the first week of chemoradiation (P < 0.01). When pretreatment ADC value was used for predicting treatment response, the area under the receiver operating characteristic curve was 0.80 with a sensitivity of 65% and a specificity of 86%. However, change in ADC within the first week of chemoradiation therapy resulted in an area under the receiver operating characteristic curve of 0.88 with 86% sensitivity and 83% specificity for prediction of treatment response.
These results suggest that ADC can be used as a marker for prediction and early detection of response to concurrent chemoradiation therapy in HNSCC.
Clinical Cancer Research 02/2009; 15(3):986-94. · 7.74 Impact Factor
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ABSTRACT: An effective method for in vivo detection of early therapeutic response of patients with non-Hodgkin's lymphoma would enable personalized clinical management of cancer therapy and facilitate the design of optimal treatment regimens. This study evaluates the feasibility of T(2)-weighted MRI (T2WI) and diffusion-weighted MRI (DWI) for in vivo detection of response of human diffuse large B-cell lymphoma xenografts in severe combined immunodeficient mice to chemotherapy. Each cycle of combination chemotherapy with cyclophosphamide, hydroxydoxorubicin, Oncovin, prednisone, and bryostatin 1 (CHOPB) was administered to tumor-carrying mice weekly for up to four cycles. T2WI and DWI were performed before the initiation of CHOPB and after each cycle of CHOPB. In order to corroborate the MRI results, histological analyses were carried out on control tumors and treated tumors after completion of all MRI studies. DWI revealed a significant (P < 0.03) increase in the mean apparent diffusion coefficient in CHOPB-treated tumors as early as 1 week after initiation of CHOPB. However, a significant (P < 0.03) decrease in mean T(2) was observed only after two cycles of CHOPB. Both MRI methods produced high-resolution (0.1 x 0.1 x 1.0 mm(3)) maps of regional therapeutic response in the treated tumors based on local apparent diffusion coefficient and T(2). Only a specific region of the tumors (in 3 of the 5 tumors) corresponding to about one third of the tumor volume exhibited a response-associate increase in ADC and decrease in T(2). An adjacent region exhibited an increase in T(2) and no change in ADC. The rest of the tumor was indistinguishable from sham-treated controls by MRI criteria. The therapeutic response of the treated tumors detected by MRI was accompanied by changes in tumor cell density, proliferation and apoptosis revealed by histological studies performed upon completion of the longitudinal study. The mechanism producing the regional response of the tumor remains to be elucidated.
NMR in Biomedicine 12/2008; 21(10):1021-9. · 3.21 Impact Factor
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ABSTRACT: In order to identify early (1)H MRS metabolic markers of response to rituximab immunotherapy and to rituximab plus CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone) combination therapy, we performed an in vivo MRS investigation of a non-Hodgkin's lymphoma (NHL) xenograft model. Human WSU-DLCL2 NHL cells were subcutaneously implanted into flanks of female severe combined immunodeficient mice. When tumor volumes reached approximately 600 mm(3), rituximab was administered for three weekly cycles at a dose of 25 mg/kg per cycle with or without CHOP. Before and after treatment, tumor lactate (Lac) and total choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated echo acquisition mode sequence, respectively. Rituximab produced a small tumor growth delay ( approximately 5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to approximately 20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H(2)O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H(2)O ratio had not changed (P = 0.58). Both Lac/H(2)O and tCho/H(2)O had decreased after one cycle of RCHOP treatment (26%, P = 0.001; 10%, P = 0.016, respectively). After two cycles of RCHOP, Ki67 assay of histological tumor specimens indicated approximately 40% decrease in proliferation (P < 0.001) in the RCHOP-treated tumors; no change was detected after treatment with rituximab alone. This study suggests that decreases in tCho/H(2)O are more sensitive indices of response to rituximab, whereas decreases in Lac/H(2)O are more sensitive to response to CHOP combination therapy.
NMR in Biomedicine 12/2008; 22(3):259-65. · 3.21 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the effect of gadolinium (III) diethyltriaminepenta-acetic acid (Gd-DTPA) mixed with a fixative on the image contrast between the white and gray matter of the perfusion-fixed mouse brain. A series of microscopic MRI (microMRI) studies using different concentrations of Gd-DTPA were performed at multiple time points to determine the optimal Gd-DTPA concentration and fixation time necessary to maximize the contrast-to-noise ratio between the white and gray matter with relatively short scan time using a three-dimensional gradient-echo pulse sequence. On the basis of the experimental results, high-resolution (39 microm isotropic) images with excellent contrast-to-noise ratio ( approximately 50) were acquired in less than 2 h of scan time after the specimen had been soaked in 10 mM Gd-DTPA for 4 days. Excellent correlation was noted between microMRI and histology in that the microMRI clearly depicted brain regions that were also observed by the Kluver-Barrera stain. The enhanced contrast between the white and gray matter obtained by the proposed microMRI method may facilitate the development of microMRI-based morphological phenotyping methods for mouse models of neurological disorders.
NMR in Biomedicine 12/2008; 22(3):303-9. · 3.21 Impact Factor
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Sanjeev Chawla,
Laura Oleaga,
Sumei Wang,
Jaroslaw Krejza,
Ronald L Wolf,
John H Woo,
Donald M O'Rourke,
Kevin D Judy,
Michael S Grady,
Elias R Melhem, Harish Poptani
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ABSTRACT: Preoperative differentiation of astrocytomas from oligodendrogliomas is clinically important, as oligodendrogliomas are more sensitive to chemotherapy. The purpose of this study was to assess the role of proton magnetic resonance spectroscopy in distinguishing astrocytomas from oligodendrogliomas.
Forty-six patients [astrocytomas (n= 17) and oligodendrogliomas (n= 29)] underwent magnetic resonance imaging and multi voxel proton magnetic resonance spectroscopic imaging before treatment. Peak areas for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (mI), glutamate/glutamine (Glx), and lipids + lactate (Lip+Lac) were analyzed from voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to Cr from each voxel. The average metabolite/Cr ratios from these voxels were then compared between astrocytomas and oligodendrogliomas. Receiver-operating curve analyses were used as measures of differentiation accuracy of metabolite ratios. A threshold value for a metabolite ratio was estimated by maximizing the sum of sensitivity and specificity.
A significant difference in mI/Cr was observed between astrocytomas and oligodendrogliomas (.50 +/- .18 vs. 0.66 +/- 0.20, P < .05). Using a threshold value of .56 for mI/Cr ratio, it was possible to differentiate oligodendrogliomas from astrocytomas with a sensitivity of 72.4% and specificity of 76.4%.
These results suggest that mI/Cr might aid in distinguishing oligodendrogliomas from astrocytomas.
Journal of neuroimaging: official journal of the American Society of Neuroimaging 11/2008; 20(1):3-8. · 1.72 Impact Factor
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ABSTRACT: The study was performed to evaluate the effect of magnetic resonance imaging (MRI) contrast agent (super paramagnetic iron oxide [SPIO]) on differentiation and migration of primary murine neural stem cells (NSCs) in comparison to a neural stem cell line (C17.2). Because detection of labeled cells depends on the concentration of SPIO particles per imaging voxel, the study was performed at various concentrations of SPIO particles to determine the concentration that could be used for in vivo detection of small clusters of grafted cells.
Murine primary NSCs or C17.2 cells were labeled with different concentrations of SPIO particles (0, 25, 100, and 250 microg Fe/mL) and in vitro assays were performed to assess cell differentiation. In vivo MRI was performed 7 weeks after neonatal transplantation of labeled cells to evaluate the difference in migration capability of the two cell populations.
Both the primary NSCs and the C17.2 cells differentiated to similar number of neurons (Map2ab-positive cells). Similar patterns of engraftment of C17.2 cells were seen in transplanted mice regardless of the SPIO concentration used. In vivo MRI detection of grafted primary and C17.2 cells was only possible when cells were incubated with 100 microg/mL or higher concentration of SPIO. Extensive migration of C17.2 cells throughout the brain was observed, whereas the migration of the primary NSCs was more restricted.
Engraftment of primary NSCs can be detected noninvasively by in vivo MRI, and the presence of SPIO particles do not affect the viability, differentiation, or engraftment pattern of the donor cells.
Academic radiology 11/2008; 15(10):1269-81. · 2.09 Impact Factor
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ABSTRACT: Cellular transplantation in the form of bone marrow has been one of the primary treatments of many lysosomal storage diseases (LSDs). Although bone marrow transplantation can help central nervous system manifestations in some cases, it has little impact in many LSD patients. Canine models of neurogenetic LSDs provide the opportunity for modeling central nervous system transplantation strategies in brains that more closely approximate the size and architectural complexity of the brains of children. Canine olfactory bulb-derived neural progenitor cells (NPCs) isolated from dog brains were expanded ex vivo and implanted into the caudate nucleus/thalamus or cortex of allogeneic dogs. Canine olfactory bulb-derived NPCs labeled with micron-sized superparamagnetic iron oxide particles were detected by magnetic resonance imaging both in vivo and postmortem. Grafts expressed markers of NPCs (i.e. nestin and glial fibrillary acidic protein), but not the neuronal markers Map2ab or beta-tubulin III. The NPCs were from dogs with the LSD mucopolysaccharidosis VII, which is caused by a deficiency of beta-glucuronidase. When mucopolysaccharidosis VII canine olfactory bulb-NPCs that were genetically corrected with a lentivirus vector ex vivo were transplanted into mucopolysaccharidosis VII recipient brains, they were detected histologically by beta-glucuronidase expression in areas identified by antemortem magnetic resonance imaging tracking. These results demonstrate the potential for ex vivo stem cell-based gene therapy and noninvasive tracking of therapeutic grafts in vivo.
Journal of Neuropathology and Experimental Neurology 10/2008; 67(10):954-62. · 4.26 Impact Factor
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ABSTRACT: The purpose of this study is to determine whether diffusion tensor imaging (DTI) metrics including tensor shape measures such as linear and planar anisotropy coefficients (CL and CP) can help differentiate glioblastomas from solitary brain metastases. Sixty-three patients with histopathologic diagnosis of glioblastomas (22 men, 16 women, mean age 58.4 years) and brain metastases (13 men, 12 women, mean age 56.3 years) were included in this study. Contrast-enhanced T1-weighted, fluid-attenuated inversion recovery (FLAIR) images, fractional anisotropy (FA), apparent diffusion coefficient (ADC), CL and CP maps were co-registered and each lesion was semi-automatically subdivided into four regions: central, enhancing, immediate peritumoral and distant peritumoral. DTI metrics as well as the normalized signal intensity from the contrast-enhanced T1-weighted images were measured from each region. Univariate and multivariate logistic regression analyses were employed to determine the best model for classification. The results demonstrated that FA, CL and CP from glioblastomas were significantly higher than those of brain metastases from all segmented regions (p<0.05), and the differences from the enhancing regions were most significant (p<0.001). FA and CL from the enhancing region had the highest prediction accuracy when used alone with an area under the curve of 0.90. The best logistic regression model included three parameters (ADC, FA and CP) from the enhancing part, resulting in 92% sensitivity, 100% specificity and area under the curve of 0.98. We conclude that DTI metrics, used individually or combined, have a potential as a non-invasive measure to differentiate glioblastomas from metastases.
NeuroImage 10/2008; 44(3):653-60. · 5.89 Impact Factor
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ABSTRACT: To identify 1H-MRS molecular biomarkers of early clinical therapeutic response in non-Hodgkin's lymphoma, an in vivo longitudinal study was performed on human non-Hodgkin's diffuse large B-cell lymphoma xenografts (WSU-DLCL2) grown in the flanks of female SCID mice. 31P-MRS measurements, which have been demonstrated to be prognostic clinical indices of response (Arias-Mendoza et al. Acad. Radiol. 2004; 11: 368-376) but which provide lower spatial resolution, were included for comparison. The animals received CHOP (cyclophosphamide, hydroxydoxorubicin, oncovin and prednisone) chemotherapy for three 1-week cycles, resulting in stable disease based on tumor volume. Localization of total choline and phosphorus metabolites in vivo was achieved with stimulated echo acquisition mode and image selected in vivo spectroscopy sequences, respectively. Significant decreases in lactate were detected by the selective multiple quantum coherence spectral editing technique after the first cycle of CHOP, whereas total choline and the phosphomonoester/nucleoside triphosphate ratio did not change until the third cycle. Ex vivo extract MRS of tumors corroborated the in vivo results. Histological staining with antibodies to Ki67 revealed a decrease in proliferation rate in CHOP-treated tumors that coincided with the decrease in lactate. This study demonstrates the utility of lactate as an early proliferation-sensitive indicator of therapeutic response in a mouse model of non-Hodgkin's lymphoma and serves as a basis for future clinical implementation of these methods.
NMR in Biomedicine 05/2008; 21(7):723-33. · 3.21 Impact Factor
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ABSTRACT: Radial MRI is typically used for scans that are sensitive to unavoidable motion. While the translational motion artifact can be easily removed from the radial trajectory data by phase correction, correction of rotational motion still remains a challenge in radial MRI. We present a novel method to refocus the image corrupted by view-to-view motion in the view-interleaved radial MRI data. In this method, the error in rotational view angles was modeled as a polynomial function of the view order and the model parameters were estimated by minimizing the self-navigator image metrics such as image entropy, gradient entropy, normalized gradient squared and mean square difference. Translational motion correction was conducted by aligning the projection profiles. Simulation studies were conducted to demonstrate the robustness of both translational and rotational motion correction methods in different noise levels. The proposed method was successfully applied to correct for motion of healthy subjects. Substantial motion correction with relative error of less than 5% was achieved by using either first- or second-order model with the image metrics. This study demonstrates the potential of the method for motion-sensitive applications.
Magnetic Resonance Imaging 05/2008; 26(3):367-78. · 1.99 Impact Factor
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ABSTRACT: Diffusion tensor imaging (DTI) and its metrics, such as mean diffusivity (MD) and fractional anisotropy (FA), have been used to detect the extent of brain tumors and understand tumor growth and its influence on the surrounding tissue. However, there are conflicting reports on how DTI metrics can be used for tumor diagnosis. The physiological interpretation of these metrics in terms of tumor growth is also not clear. The objective of this study was to investigate the DTI parameters in two rat brain tumor models (9L and F98) with different patterns of aggressiveness by longitudinal monitoring of tumor growth and comparing the DTI parameters of these two tumor models. In addition to the standard DTI metrics, MD and FA, we measured other metrics representing diffusion tensor shape, such as linear and planar anisotropy coefficients (CL and CP), and orientational coherence measured by lattice index (LI), to characterize the two tumor models. The 9L tumor had higher FA, CL, and LI than the F98 tumor. F98 had a larger difference in anisotropies between tumor and peritumor regions than 9L. From the eigenvalues, it was found that the increase in CL and trace of the 9L tumor was due to an increase in the primary eigenvalue, whereas the increase in CP in the peritumor region was due to an increase in both primary and secondary eigenvalues and a decrease in tertiary eigenvalue. Our results indicate that shape-oriented anisotropy measures, such as CL and CP, and orientational coherence measures, such as LI, can provide useful information in differentiating these two tumor models and also differentiating tumor from peritumoral regions.
NMR in Biomedicine 04/2008; 21(3):208-16. · 3.21 Impact Factor
