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ABSTRACT: Typically, magnetic resonance imaging (MRI) analysis is performed on magnitude data, and multiple echo T2 data consist of numerous images of the same slice taken with different echo spacing, giving voxel-wise temporal sampling of the noise as the signals decay according to T2 relaxation. Magnitude T2 decay data has Rician distributed noise which is characterized by a change in the noise distribution from Gaussian, through a transitional region, to Rayleigh as the signal to noise ratio decreases with increasing echo time. Non-Gaussian noise distributions may produce errors in the commonly applied non-negative least squares (NNLS) algorithm that is used to assess multiple echo decays for compartmentalized water environments through the creation of T2 distributions. Typically, Gaussian noise is sought by performing spatial-based phase correction on the MRI data however, these methods cannot capitalize on the temporal information available from multiple echo T2 acquisitions. Here we describe a temporal phase correction (TPC) algorithm that utilizes the temporal noise information available in multiple echo T2 acquisitions to put the relevant decay information in the Real portion of the decay data and leave only noise in the Imaginary portion. We apply this TPC algorithm to create real-valued multiple echo T2 data from human subjects measured at 1.5T. We show that applying TPC causes changes in the T2 distribution estimates; notably the possible resolution of separate extracellular and intracellular water environments, and the disappearance of the commonly labeled cerebrospinal fluid peak, which might be an artefact observed in many previously published multiple echo T2 analyses.
Journal of Magnetic Resonance 03/2013; 231C:22-31. · 2.14 Impact Factor
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ABSTRACT: PURPOSE: To measure the arterial input function (AIF) in a mouse tail at high temporal resolution with signal phase of MR projections. METHODS: The technique involves the acquisition of one 2D image before injection, followed by a series of projections before, during, and after contrast injection. Differences in the signal phase, relative to the mean preinjection phase, were calculated and converted into a concentration of Gd. RESULTS: An AIF with a temporal resolution of 100 ms was measured and verified with colorimetry (in a flow phantom) and mass spectrometry analysis (in vivo). The projection-based AIF is expected to better represent the rapid contrast kinetics in the blood following injection, thus improving the accuracy of quantitative dynamic contrast-enhanced-MRI analysis. Colorimetry experiments confirmed that signal phase is preferred over magnitude for a precise determination of an AIF. In-vivo experiments demonstrate the feasibility of our approach in mice. CONCLUSION: AIFs can be measured quickly and precisely using phase from projections. Phase data are sensitive to the flow velocity; but this sensitivity is significantly reduced when flow compensation was used. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 02/2013; · 2.96 Impact Factor
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ABSTRACT: Although multiple sclerosis (MS) lesions have been studied extensively using histology and magnetic resonance imaging (MRI), little is known about diffusely abnormal white matter (DAWM). Diffusely abnormal white matter, regions with reduced mild MRI hyperintensity and ill-defined boundaries, show reduced myelin water fraction, and decreased Luxol fast blue staining of myelin phospholipids, with relative preservation of myelin basic protein and 2',3'-cyclic-nucleotide 3'-phosphohydrolase. Because DAWM may be important in MS disability and progression, further histologic characterization is warranted. The MRI data were collected on 14 formalin-fixed MS brain samples that were then stained for myelin phospholipids, myelin proteins, astrocytes and axons. Diffusely abnormal white matter showed reduced myelin water fraction (-30%, p < 0.05 for 13 samples). Myelin phospholipids showed the most dramatic and consistent histologic reductions in staining optical density (-29% Luxol fast blue and -24% Weil's, p < 0.05 for 13 and 14 samples, respectively) with lesser myelin protein involvement (-11% myelin-associated glycoprotein, -10% myelin basic protein, -8% myelin-oligodendrocyte glycoprotein, -7% proteolipid protein, -5% 2',3'-cyclic-nucleotide 3'-phosphohydrolase, p < 0.05 for 3, 3, 1, 2, and 3 samples, respectively). Axonal involvement was intermediate. Diffusely abnormal white matter lipid and protein reductions occurred independently. These findings suggest a primary lipid abnormality in DAWM that exceeds protein loss and is accompanied by axonal degeneration. These phenomena may be important in MS pathogenesis and disease progression, which is prominent in individuals with DAWM.
Journal of neuropathology and experimental neurology. 12/2012;
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ABSTRACT: To develop an image-based technique capable of detection and grading of prostate cancer, which combines features extracted from multiparametric MRI into a single parameter map of cancer probability.
A combination of features extracted from diffusion tensor MRI and dynamic contrast enhanced MRI was used to characterize biopsy samples from 29 patients. Support vector machines were used to separate the cancerous samples from normal biopsy samples and to compute a measure of cancer probability, presented in the form of a cancer colormap. The classification results were compared with the biopsy results and the classifier was tuned to provide the largest area under the receiver operating characteristic (ROC) curve. Based solely on the tuning of the classifier on the biopsy data, cancer colormaps were also created for whole-mount histopathology slices from four radical prostatectomy patients.
An area under ROC curve of 0.96 was obtained on the biopsy dataset and was validated by a "leave-one-patient-out" procedure. The proposed measure of cancer probability shows a positive correlation with Gleason score. The cancer colormaps created for the histopathology patients do display the dominant tumors. The colormap accuracy increases with measured tumor area and Gleason score.
Dynamic contrast enhanced imaging and diffusion tensor imaging, when used within the framework of supervised classification, can play a role in characterizing prostate cancer.
Journal of Magnetic Resonance Imaging 01/2012; 35(6):1403-13. · 2.70 Impact Factor
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ABSTRACT: Specific bioprobes for single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) have enormous potential for use in cancer imaging in near-future clinical settings. The authors describe the development of dual modality molecular imaging bioprobes, in the form of magnetic nanoparticles (NPs) conjugated to antibodies, for SPECT and MRI of mesothelin-expressing cancers. The bioprobes were developed by conjugating (111)In labeled antimesothelin antibody mAbMB to superparamagnetic iron oxide NPs. Our experimental findings provide evidence that such bioprobes retain their magnetic properties as well as the ability to specifically localize in mesothelin-expressing tumors. It is anticipated that combining SPECT with MR will help obtain both functional and anatomical imaging information with high signal sensitivity and contrast, thereby providing a powerful diagnostic tool for early diagnosis and treatment planning of mesothelin-expressing cancers.
Nanomedicine: nanotechnology, biology, and medicine 11/2011; 8(6):1007-16. · 5.44 Impact Factor
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ABSTRACT: Chemotherapy for glioblastoma (GBM) patients is compromised in part by poor perfusion in the tumor. The present study evaluates how treatment with liposomal formulation of irinotecan (Irinophore C™), and other liposomal anticancer drugs, influence the tumor vasculature of GBM models grown either orthotopically or subcutaneously.
Liposomal vincristine (2 mg/kg), doxorubicin (Caelyx®; 15 mg/kg) and irinotecan (Irinophore C™; 25 mg/kg) were injected intravenously (i.v.; once weekly for 3 weeks) in Rag2M mice bearing U251MG tumors. Tumor blood vessel function was assessed using the marker Hoechst 33342 and by magnetic resonance imaging-measured changes in vascular permeability/flow (Ktrans). Changes in CD31 staining density, basement membrane integrity, pericyte coverage, blood vessel diameter were also assessed.
The three liposomal drugs inhibited tumor growth significantly compared to untreated control (p < 0.05-0.001). The effects on the tumor vasculature were determined 7 days following the last drug dose. There was a 2-3 fold increase in the delivery of Hoechst 33342 observed in subcutaneous tumors (p < 0.001). In contrast there was a 5-10 fold lower level of Hoechst 33342 delivery in the orthotopic model (p < 0.01), with the greatest effect observed following treatment with Irinophore C. Following treatment with Irinophore C, there was a significant reduction in Ktrans in the orthotopic tumors (p < 0.05).
The results are consistent with a partial restoration of the blood-brain barrier following treatment. Further, treatment with the selected liposomal drugs gave rise to blood vessels that were morphologically more mature and a vascular network that was more evenly distributed. Taken together the results suggest that treatment can lead to normalization of GBM blood vessel the structure and function. An in vitro assay designed to assess the effects of extended drug exposure on endothelial cells showed that selective cytotoxic activity against proliferating endothelial cells could explain the effects of liposomal formulations on the angiogenic tumor vasculature.
BMC Cancer 01/2011; 11:124. · 3.01 Impact Factor
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ABSTRACT: To develop a device for sectioning prostatectomy specimens that would facilitate comparison between histology and in vivo MRI.
A multi-bladed cutting device was developed, which consists of an adjustable box capable of accommodating a prostatectomy specimen up to 85 mm in size in the lateral direction, a "plunger" tool to press on the excised gland from the top to prevent it from rolling or sliding during sectioning, and a multi-bladed knife assembly capable of holding up to 21 blades at 4-mm intervals. The device was tested on a formalin fixed piece of meat and subsequently used to section a prostatectomy specimen. Histology sections were compared with T2-weighted MR images acquired in vivo before the prostatectomy procedure.
The prostatectomy specimen slices were very uniform in thickness with each face parallel to the other with no visible sawing marks on the sections by the blades after the cut. MRI and histology comparison showed good correspondence between the two images.
The developed device allows sectioning of prostatectomy specimens into parallel cuts at a specific orientation and fixed intervals. Such a device is useful in facilitating accurate correlation between histology and MRI data.
Journal of Magnetic Resonance Imaging 10/2010; 32(4):992-6. · 2.70 Impact Factor
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ABSTRACT: The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) has not been elucidated in detail, but may be an important element in disability and clinical progression.
Fifty-three subjects with MS were examined with T₁, multi-echo T₂ and magnetization transfer (MT). Twenty-three samples of formalin-fixed MS brain tissue were examined with multi-echo T₂ and subsequently stained for myelin phospholipids using luxol fast blue, for axons using Bielschowsky, immunohistochemically for the myelin proteins myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3' phosphohydrolase (CNP) and for astrocytes using glial fibrillary acidic protein (GFAP). Regions of interest in DAWM were compared with normal appearing white matter.
Fourteen of 53 subjects with MS in the in vivo study showed the presence of DAWM. Subjects with DAWM were found to have a significantly lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD) when compared with subjects without DAWM (EDSS: 1.5 versus 3.0, p = 0.031; DD: 5.4 versus 10.3 years, p = 0.045). DAWM in vivo had reduced myelin water and MT ratio, and increased T₂ and water content. Histological analysis suggests DAWM, which shows a reduction of the myelin water fraction, is characterized by selective reduction of myelin phospholipids, but with a relative preservation of myelin proteins and axons.
These findings suggest that the primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids that correlates with a reduction of the myelin water fraction.
Multiple Sclerosis 10/2010; 17(2):144-50. · 4.26 Impact Factor
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ABSTRACT: To test whether individually measured arterial input function (AIF) provides more accurate prostate cancer diagnosis then population average AIF when dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data are acquired with limited temporal resolution.
Twenty-six patients with a high clinical suspicion for prostate cancer and no prior treatment underwent DCE MRI examination at 3.0 T before biopsy. DCE MRI data were fitted to a pharmacokinetic model using three forms of AIF: an individually measured, a local population average, and a literature double exponential population average. Receiver operating characteristic (ROC) analysis was used to correlate MRI with the biopsy results. Goodness of fit (chi(2)) for the three AIFs was compared using nonparametric Mann-Whitney test.
Average volume transfer constant (K(trans)) values were significantly higher in tumor than in normal peripheral zone for all three AIFs. The individually measured and the local population average AIFs had the highest sensitivity (76%), whereas the double exponential AIF had the highest specificity (82%). The areas under the ROC curves were not significantly different between any of the AIFs (0.81, 0.76, and 0.81 for the individually measured, local population average, and double exponential AIFs, respectively). chi(2) was not significantly different for the three AIFs; however, it was significantly higher in enhancing than in nonenhancing regions for all three AIFs.
These results suggest that, when DCE MRI data are acquired with limited temporal resolution, experimentally measured individual AIF is not significantly better than population average AIF in predicting the biopsy results in prostate cancer.
Academic radiology 04/2010; 17(4):520-5. · 2.09 Impact Factor
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ABSTRACT: The purpose of this work was to compare diagnostic accuracy of Diffusion Tensor Imaging (DTI), dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and their combination in diagnosing prostate cancer. Twenty-five patients with clinical suspicion of prostate cancer underwent MRI, prior to transrectal ultrasound-guided biopsies. MRI data were correlated to biopsy results. Logistic regression models were constructed for the DTI parameters, DCE MRI parameters, and their combination. The areas under the receiver operator characteristic curves (AUC) were compared between the models. The nonparametric Wilcoxon signed rank test was used for statistical analysis. The sensitivity and specificity values were respectively 81% (74-87%) and 85% (79-90%) for DTI and 63% (55-70%) and 90% (85-94%) for DCE. The combination "DTI or DCE MRI" had 100% (97-100%) sensitivity and 77% (69-83%) specificity, while "DTI and DCE MRI" had 44% (37-52%) sensitivity and 98% (94-100%) specificity. The AUC for DTI+DCE parameters was significantly higher than that for either DTI (0.96 vs. 0.92, P=.0143) or DCE MRI parameters (0.96 vs. 0.87, P=.00187) alone. In conclusion, the combination of DTI and DCE MRI has significantly better accuracy in prostate cancer diagnosis than either technique alone.
Magnetic Resonance Imaging 04/2010; 28(5):621-8. · 1.99 Impact Factor
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ABSTRACT: Tears of the acetabular labrum are frequently present in patients with groin pain. While it is clear that the labrum contributes to the surface area articulating with the femoral head, it is not clear whether labral repair yields different load distribution in the hip compared to labral resection.
Determine whether labral repair reduces cartilage strain more effectively than labral resection.
Six human cadaveric hips (mean age 37 years) were loaded in a simulated single-leg stance within the bore of a 7T MR scanner. After cartilage had reached a steady-state thickness distribution, a scan of the cartilage was acquired with a voxel size of 0.1x0.1x0.3mm. This method was repeated for each of six specimens when the labrum was intact, after a surgically simulated labral tear, after an arthroscopic labral repair and after labral resection. Cartilage thickness and strain in an anterosuperior region of interest were measured from the MR scans. A paired t-test was used to compare mean and maximum cartilage strain when the labrum was intact vs. torn, torn vs. repaired and repaired vs. resected. Three-dimensional patterns of cartilage strain distribution were qualitatively compared for the different labral conditions.
For the number of specimens tested we found no change in mean and maximum cartilage strain, and little obvious change in the pattern of cartilage strain distribution after a simulated labral tear. Labral repair caused a 2% decrease in mean cartilage strain compared to a torn labrum (p=0.014). Labral resection caused a 4% and 6% increase in mean and maximum cartilage strain, respectively, compared to labral repair (p=0.02), and the cartilage strain distribution was elevated throughout the region of interest.
Based on our ex vivo findings of increased cartilage strain after labral resection when compared to labral repair, we have demonstrated the associated consequences to the mechanical environment of the cartilage following surgical treatment of the labrum.
Journal of biomechanics 12/2009; 43(5):858-63. · 2.66 Impact Factor
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ABSTRACT: The mechanism of action of deep brain stimulation (DBS) in the alleviation of tremor in multiple sclerosis (MS) and other neurological disorders is unknown. Moreover, whether the trauma accompanying this surgery is responsible for the induction of new MS plaques is controversial. Here we report the first description of the post-mortem imaging and pathologic findings in the brain of a MS patient who underwent thalamic DBS for the treatment of MS-induced tremor. MR imaging of formalin-fixed brain slices was carried out at 1.5, 3 and 7 Tesla and correlated with the histopathology. There were numerous demyelinative plaques in the white mater, cortex and deep gray matter. There were no plaques along the DBS tract within the sections that sampled the deep hemispheric white matter. However, deep within the thalamus focal demyelination approximated the tract, particularly in the region corresponding to the electrical field. The findings in this single case raise the possibility that focal demyelination may be induced by the electrical field and this may be responsible for long-lasting alleviation of tremor in the absence of continued electrostimulation.
Multiple Sclerosis 10/2009; 15(11):1311-21. · 4.26 Impact Factor
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ABSTRACT: Cardiometabolic risk factors are sorely underreported after spinal cord injury (SCI), despite the high prevalence of metabolic disorders and cardiovascular mortality in this population. Body-composition analysis and serum-lipid profiling are two assessments that are beginning to be more widely used to document metabolic changes after clinical SCI. Individuals with SCI have been reported to carry increased visceral fat and to exhibit altered serum-lipid levels. However, little is known about the development of these cardiometabolic risk factors in animal models. Using a combination of magnetic resonance imaging (MRI) and adipose tissue dissection, we show that visceral and subcutaneous adipose tissue were both increased at 1 month, but not at 1 week, after complete T3 SCI in rats. Additionally, at 1 month post injury, T3 SCI rats exhibited nonfasting serum hypertriglyceridemia, a result obtained using both standard clinical methods and a home cholesterol monitoring device (CardioChek). Interestingly, at 1 month post injury, rats with complete T10 SCI did not show an increase in either visceral adiposity or serum triglyceride levels. The fact that complete high-thoracic SCI disrupts lipid metabolism and perturbs fat storage in the subacute period, while low-thoracic SCI does not, suggests that differences in descending sympathetic control of adipose tissue might play a role in these changes. These results provide the first evidence of cardiometabolic risk factors in experimental animals with SCI, and are a starting point for investigations of the etiology of obesity and metabolic dysfunctions that often accompany SCI.
Journal of neurotrauma 09/2009; 27(1):275-85. · 4.25 Impact Factor
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Jennifer H E Baker,
Jeffrey Lam,
Alaistair H Kyle,
Jonathan Sy,
Thomas Oliver,
Steven J Co,
Wieslawa H Dragowska,
Euan Ramsay,
Malathi Anantha,
Thomas J Ruth,
Michael J Adam,
Andrew Yung, Piotr Kozlowski,
Andrew I Minchinton,
Sylvia S W Ng,
Marcel B Bally,
Donald T T Yapp
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ABSTRACT: To examine the antitumor effects of Irinophore C, a nanopharmaceutical formulation of irinotecan, on the tissue morphology and function of tumor vasculature in HT-29 human colorectal tumors.
Fluorescence microscopy was used to map and quantify changes in tissue density, tumor vasculature, hypoxia, and the distribution of Hoechst 33342, a perfusion marker, and the anticancer drug, doxorubicin. Noninvasive magnetic resonance imaging was used to quantify Ktrans, the volume transfer constant of a solute between the blood vessels and extracellular tissue compartment of the tumor, as a measure of vascular function. Following treatment with Irinophore C, 19F magnetic resonance spectroscopy was used to monitor the delivery of 5-fluorouracil (5-FU) to the tumor tissue, whereas scintigraphy was used to quantify the presence of bound [14C]5-FU.
Irinophore C decreased cell density (P = 8.42 x 10(-5)), the overall number of endothelial cells in the entire section (P = 0.014), tumor hypoxia (P = 5.32 x 10(-9)), and K(trans) (P = 0.050). However, treatment increased the ratio of endothelial cells to cell density (P = 0.00024) and the accumulation of Hoechst 33342 (P = 0.022), doxorubicin (P = 0.243 x 10(-5)), and 5-FU (P = 0.0002) in the tumor. Vascular endothelial growth factor and interleukin-8, two proangiogenic factors, were down-regulated, whereas the antiangiogenic factor TIMP-1 was up-regulated in Irinophore C-treated tumors.
Irinophore C treatment improves the vascular function of the tumor, thereby reducing tumor hypoxia and increasing the delivery and accumulation of a second drug. Reducing hypoxia would enhance radiotherapy, whereas improving delivery of a second drug to the tumor should result in higher cell kill.
Clinical Cancer Research 12/2008; 14(22):7260-71. · 7.74 Impact Factor
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ABSTRACT: ABSTRACT Diffusion tensor imaging (DTI) and quantitative T(2) magnetic resonance imaging (MRI) were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. Luxol Fast Blue (LFB) and myelin basic protein (MBP) staining was used to assess myelin damage, and neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining was used to assess axonal damage. Average values of myelin water fraction (MWF), fractional anisotropy (FA), longitudinal diffusivity (D(long)), transverse diffusivity (D(trans)), and average diffusivity (D(ave)) were calculated in the fasciculus gracilis, fasciculus cuneatus, and the dorsal corticospinal tract (CST) 5 mm cranial, as well as 5 and 10 mm caudal to injury and correlated with histology. These tracts were selected as these contain bundles of parallel ascending and descending axons in very circumscribed areas with little intermingling of other axonal populations. Axonal and myelin degeneration occur cranial to injury in the funiculus gracilis and caudal to injury in the CST. Both MWF and D(trans) showed significant correlation with LFB staining at 3 weeks (0.64 and -0.49, respectively) and 8 weeks post-injury (0.88 and -0.71, respectively). Both D(long) and FA correlated significantly with NF/Tub staining at 3 weeks post-injury (0.78 and 0.64, respectively), while only D(long) displayed significant correlation 8 weeks post-injury (0.58 and 0.33, respectively). This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord.
Journal of Neurotrauma 07/2008; 25(6):653-76. · 3.65 Impact Factor
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ABSTRACT: Myelin water imaging (MWI) promises to be invaluable in understanding neurological diseases like MS. However, a limitation of MWI is signal to noise ratio. Recently, a number of investigators have performed MWI at field strengths higher than 1.5 T. Our goal was to determine if myelin water imaging at increased SNR, arising from the use of a small bore 7 T MR system with optimized coil geometry, enables the production of superior myelin water maps with increased spatial detail and enables better correlations with histology. Ten formalin-fixed MS brain samples underwent a 32-echo T(2) relaxation experiment which measured myelin water fraction (MWF) on a 7-T animal MRI scanner. MWF correlated strongly qualitatively and quantitatively with luxol fast blue staining for myelin [mean (range): R(2)=0.78 (0.56-0.95), p<0.0001]. The quality and detail of 7 T myelin water maps were far superior to that previously seen at 1.5 T, allowing for visualization of fine structures such as the normal prominent myelination of the deeper cortical layers, the alveus of the hippocampus and rings of preserved myelin in a concentric Balo's lesion. 7 T imaging will allow detailed assessment of myelin pathology to a degree not possible with lower field strengths.
NeuroImage 06/2008; 40(4):1575-80. · 5.89 Impact Factor
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ABSTRACT: Multiecho imaging data were acquired at 7T from control and injured (dorsal column transection) rat spinal cords ex vivo with in-plane resolution of 61, 78, and 100 microm, and from a control rat spinal cord in vivo with in-plane resolution of 117 microm. The myelin water maps were calculated using nonnegative least-squares (NNLS) analysis of the decay curves. For the control cords, myelin water maps showed details of the cord morphology, and the average myelin water fraction (MWF) values in white matter and gray matter corresponded well with previously published results and the expected amounts of myelin within the cord, and correlated very well with Luxol Fast Blue stain (R(2)=0.95). Myelin water maps from an injured cord showed excellent qualitative correlation with histology. This pilot study demonstrates that high-resolution myelin water mapping in rat spinal cord is feasible, and this technique has potential to be a valuable tool in studying white matter damage in rat models of spinal cord injury.
Magnetic Resonance in Medicine 05/2008; 59(4):796-802. · 2.96 Impact Factor
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ABSTRACT: (19)F magnetic resonance spectroscopy (MRS) was used to non-invasively detect EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] adducts in the Shionogi tumour model of prostate cancer to evaluate hypoxia.
(19)F MRS signal of EF5 in Shionogi mouse tumours was acquired using a 2 cm diameter solenoid volume coil with a 7.05 T Bruker scanner. MRS signal was observed in mouse tumours longitudinally following intraperitoneal (IP) injection of EF5. Another mouse group was injected intravenously (IV) with EF5, and in vivo MRS signal was obtained two hours after injection. This data was compared with the ex vivo percentage of hypoxic cells present in the corresponding excised tumours, determined by flow cytometry of bound EF5.
Longitudinal (19)F MRS signal attributable to EF5 began to decline within five hours of EF5 administration. Flow cytometry comparisons yielded an inverse correlation (p-value < 0.006) between the MRS signal and tumour hypoxic cell percentage. The tumours exhibited an average cell viability of 34 +/- 26%.
The results confirmed that MRS of EF5 in mice is an unsuitable technique for the determination of EF5 binding as a measure of tumour hypoxia.
International Journal of Radiation Biology 04/2008; 84(3):237-42. · 2.28 Impact Factor
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ABSTRACT: Diffusion-weighted (DW) MRI at 1.5 T was carried out in two groups of patients. MRI data were correlated with the biopsy and histopathology (where available). The performance of two sequences -- a single-shot FSE (14 patients) and a single-shot EPI (15 patients) -- was compared. Average ADC values from the normal peripheral zone (PZ), central gland (CG) and the tumour [prostate carcinoma (PCa)] were calculated from b values of 0 and 600. Tukey-Kramer test was used for statistical analysis. EPI produced higher values of ADC (10(-3) mm(2)/s) than FSE sequence: 1.992+/-0.208 vs. 1.573+/-0.270 in PZ (P<.001), 1.518+/-0.126 vs. 1.373+/-0.179 in CG and 1.214+/-0.254 vs. 0.993+/-0.158 in PCa (P<.01). In conclusion, both EPI and FSE sequences showed differences in ADC between normal PZ, CG and PCa; however, EPI produced significantly higher ADC values than FSE.
Magnetic Resonance Imaging 01/2008; 26(1):72-6. · 1.99 Impact Factor
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ABSTRACT: Pancreatic cancer is a devastating disease with no cure. Therapies that target the tumor vasculature are promising new treatment strategies. Magnetic resonance imaging (MRI) can non-invasively determine a vessel size index and a blood volume fraction to characterize the vascular compartment in a tumor. The changes in the T2 and T2* relaxation rate constants after the administration of superparamagnetic iron oxide (SPIO) particles are dependent on the size and morphology of tissue blood vessels. In this study, MRI was used to investigate changes in the tumor vasculature in an orthotopic primary human pancreatic cancer xenograft model during tumor progression. The SPIO contrast agent Feridex I.V. was first validated as an intravascular contrast agent over the course of the imaging session, and shown to remain in the blood for at least 1.5 h. The average vessel size index was not correlated to the tumor area within an image slice, but the average blood volume fraction was significantly and negatively correlated to the tumor area (p<0.05). Blood volume fraction may serve as a non-invasive biomarker for changes in the tumor vasculature due to tumor growth Further investigation is needed to evaluate this promising technique as a tool to monitor tumor vascular changes in response to antiangiogenic therapies in pancreatic cancer.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2008; 2008:851-4.
