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Prostate cancer detection with 3-T MRI: comparison of diffusion-weighted and T2-weighted imaging.

OBJECTIVE: To compare the clinical value of diffusion-weighted (DW) and T2-weighted (T2W) imaging in detecting prostate cancer using a 3-Tesla (3T) magnetic resonance (MR) system. MATERIALS AND METHODS: Thirty-seven patients with suspected prostate cancer underwent T2W and DW imaging at 3T using an 8-channel phased-array coil. These images and apparent diffusion coefficient (ADC) maps were read retrospectively and blindly. The results were compared with histopathologic findings, and receiver operating characteristic (ROC) analysis was used to compare the cancer detection performance of T2W and DW imaging. RESULTS: The areas under the ROC curves for DW imaging and T2W imaging were 0.89 and 0.82, respectively. The performance of DW imaging in prostate cancer detection was significantly better than that of T2W imaging (P=0.0371). CONCLUSION: With a 3T MR system, the performance of DW imaging in detecting prostate cancer was better than that of T2W imaging. DW imaging appears to be a robust and reliable method to examine the whole prostate within an acceptable scan time in clinical settings.

Adenocarcinoma↗

Transient MRI-detected water apparent diffusion coefficient reduction correlates with c-fos mRNA but not hsp70 mRNA induction during focal cerebral ischemia in rats.

Cerebral ischemia induces immediate early genes such as c-fos and stress genes such as hsp70. In this study, the spatial relationships between c-fos and hsp70 mRNA expression and changes detectable with diffusion and perfusion magnetic resonance (MR) imaging were examined. The middle cerebral artery (MCA) of young adult rats was occluded for 30 or 60 min. Diffusion MR (D-MR) images were acquired continuously during the ischemic period and dysprosium-contrast perfusion (P-MR) images were acquired at the end of the ischemic period. C-fos and hsp70 mRNA expression were examined with in situ hybridization. The most significant finding of this work was that for both durations of ischemia, c-fos induction was observed in cortical and sub-cortical regions exhibiting a transient reduction in the apparent diffusion coefficient of water (ADC). Transients which occurred on a time scale of 3 min may have been caused by spreading depression. Those occurring on a 10-min time scale may have been caused by an initial reduction in blood flow with occlusion that was followed by an ischemia-induced increase in collateral blood flow. P-MR imaging showed that perfusion in c-fos positive regions was higher than in regions with persistently reduced ADC. Hsp70 induction did not correlate with transient ADC reduction. It was induced in the MCA territory in regions showing persistent ADC changes, with induction being greatest at the periphery of these regions. It was also induced in regions that exhibited both spontaneous reversal of the diffusion changes and decreased perfusion.

Animals↗

MRI measurements of water diffusion and cerebral perfusion: their relationship in a rat model of focal cerebral ischemia.

The aim of this study was to examine the quantitative relationship between changes in apparent diffusion coefficient (ADC) and transverse relaxivity (delta R2*) measurements of relative perfusion deficits within the gradients of a focal ischemic insult. Sixty minutes after permanent occlusion of the middle cerebral artery, rats (n = 7) were subjected to spin echo diffusion-weighted scans followed by fast low-angle shot (FLASH) perfusion-sensitive scans. Diffusion-weighted images showed clear ischemic lesions in the affected basal ganglia and cortex. Ischemic deficits were demonstrated as a decrease in first-pass transit of injected boluses of gadodiamide. ADC maps were generated and regions of interest (ROIs) were obtained to span the range of ADC reductions from the lesion center or core to the periphery or penumbra. Corresponding ROIs from the bolus injection images were used to calculate perfusion indexes relative to contralateral levels as ratios of delta R2* integrals and ratios of delta R2* peak values. In all animals, the degree of ADC reductions was related to the degree of delta R2* perfusion deficits, ranging from severe ischemia in the core of the lesion to intermediate and moderate changes toward the lesion periphery. In the ischemic periphery, ADC reductions were linearly correlated with delta R2* peak ratios. However, no significant correlation was found between ADC reductions and delta R2* integral ratios. These data suggest that magnetic resonance measurements of ADC and delta R2* peak ratios can be used to quantitatively assess the variable gradients in focal ischemia, including potentiallyn critical areas at risk in the ischemic periphery.

Animals↗

Multiple cerebral microbleeds: MRI marker of a diffuse hemorrhage-prone state.

BACKGROUND: Recent reports have indicated that cerebral microbleeds (CMBs) detected on gradient-echo (GRF) magnetic resonance imaging may be a risk factor for therapy related intracranial hemorrhages (ICHs). CASE DESCRIPTION: The authors describe 3 patients with multiple CMBs in whom ICHs occurred either after tissue plasminogen activator administration or after the initiation of antiplatelet therapy. Hemorrhages occurred in brain areas with normal appearances on GRE imaging and remote from the CMBs. CONCLUSION: Multiple CMBs may signal a diffuse hemorrhage-prone vasculopathy.

Aged↗

Visualization of ischaemic penumbra using a computed tomography perfusion method.

A computed tomography (CT) perfusion imaging and a diffusion/perfusion magnetic resonance imaging (MRI) were performed in a 51-year-old man at 15 and 15.5 h of onset of left middle cerebral artery infarction, respectively. The established infarct, as revealed by the diffusion-weighted MRI, had low values of cerebral blood flow (CBF) and cerebral blood volume (CBV) on the CT perfusion study. The ischaemic penumbra, as reflected by the perfusion-diffusion mismatch on MRI, had reduced CBF, prolonged mean transit time (MTT) and compensated CBV. Spontaneous bleeding occurred in the medial part of the left lentiform nucleus, immediately following decompressive craniectomy. CT measurements of CBF, CBV and MTT may visualize the ischaemic penumbra and explain the site of bleeding after surgical decompression.

Brain Ischemia↗

Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be "tissue at risk." The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. METHODS: Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with "time-to-peak" (TTP) delays of >/=2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score. RESULTS: In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of >/=6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay >/=6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay >/=6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of >/=4 s correlated better with ESS (r=-0.88, P<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of approximately 4 s might be the threshold for functional impairment of brain tissue. CONCLUSIONS: Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of >/=6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays >/=4 and <6 s) appear to also contribute to the acute clinical deficit.

Acute Disease↗

Application of magnetic resonance imaging to study pathophysiology in brain disease models.

Magnetic resonance imaging (MRI) provides a noninvasive and multimodal tool to study neurological disorders in experimental models. MRI experiments can be sensitized to various contrast parameters and, hence, enable comprehensive assessment of normal and abnormal brain physiology. Different conventional and novel MRI techniques have been developed that supply specific information on lesion location and size (e.g., T2- and diffusion-weighted MRI), alterations in tissue structure (e.g., magnetization transfer imaging and diffusion tensor imaging), perfusion deficits (perfusion MRI), brain activation (functional MRI), cell migration (cellular MRI), gene expression (molecular MRI), and more. The advantages of in vivo, longitudinal, and multiparametric studies with MRI provide unique opportunities for characterizing and delineating experimental models of neurological diseases and pathophysiological mechanisms, as well as spontaneous and treatment-induced recovery mechanisms.

Animals↗

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

BACKGROUND AND PURPOSE: Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS: P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. RESULTS: On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. CONCLUSIONS: In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

Animals↗

The effect of filter size on VBM analyses of DT-MRI data.

Voxel-based morphometry (VBM) has been used to analyze diffusion tensor MRI (DT-MRI) data in a number of studies. In VBM, following spatial normalization, data are smoothed to improve the validity of statistical inferences and to reduce inter-individual variation. However, the size of the smoothing filter used for VBM of DT-MRI data is highly variable across studies. For example, a literature review revealed that Gaussian smoothing kernels ranging in size (full width at half maximum) from zero to 16 mm have been used in DT-MRI VBM type studies. To investigate the effect of varying filter size in such analyses, whole brain DT-MRI data from 14 schizophrenic patients were compared with those of 14 matched control subjects using VBM, when the filter size was varied from zero to 16 mm. Within this range of smoothing, four different conclusions regarding apparent patient control differences could be made: (i) no significant patient-control differences; (ii) reduced FA in right superior temporal gyrus (STG) in patients; (iii) reduced FA in both right STG and left cerebellum in patients; and (iv) reduced FA only in left cerebellum in patients. These findings stress the importance of recognizing the effect of the matched filter theorem on VBM analyses of DT-MRI data. Finally, we investigated whether one of the underlying assumptions of parametric VBM, i.e., the normality of the residuals, is met. Our results suggest that, even with moderate smoothing, a large number of voxels within central white matter regions may have non-normally distributed residuals thus making valid statistical inferences with a parametric approach problematic in these areas.

Adult↗

Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors.

BACKGROUND: A surrogate marker for treatment response that can be observed earlier than comparison of sequential magnetic resonance imaging (MRI) scans, which depends on relatively slow changes in tumor volume, may improve survival of brain tumor patients by providing more time for secondary therapeutic interventions. Previous studies in animals with the use of diffusion MRI revealed rapid changes in tumor water diffusion values after successful therapeutic intervention. METHODS: The present study examined the sensitivity of diffusion MRI measurements in orthotopic rat brain tumors derived from implanted rat 9L glioma cells. The effectiveness of therapy for individual brain cancer patients was evaluated by measuring changes in tumor volume on neuroimaging studies conducted 6--8 weeks after the conclusion of a treatment cycle. RESULTS: Diffusion MRI could detect water diffusion changes in orthotopic 9L gliomas after doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) that resulted in as little as 0.2 log cell kill, a measure of tumor cell death. Mean apparent diffusion coefficients in tumors were found to be correlated with and highly sensitive to changes in tumor cellularity (r =.78; two-sided P =.041). The feasibility of serial diffusion MRI in the clinical management of primary brain tumor patients was also demonstrated. Increased diffusion values could be detected in human brain tumors shortly after treatment initiation. The magnitude of the diffusion changes corresponded with clinical outcome. CONCLUSIONS: These results suggest that diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.

Adolescent↗

Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a predominantly clinical and electromyographic diagnosis. Conventional MRI reveals atrophy of the motor system, particularly the pyramidal tract, in the advanced stages but does not provide a sensitive measure of disease progression. Three patients with different principal symptoms of ALS, i.e., with predominant involvement of the upper (UMN) or lower (UMN) motor neurons, or bulbar disease, respectively, underwent serial clinical examination including lung function tests, conventional MRI, and diffusion tensor imaging (DTI). MRI demonstrated changes in of the pyramidal tract without measurable variation on follow-up. The patient with UMN involvement showed remarkable progressive loss of diffusion anisotropy in the pyramidal tract. DTI might be useful, together with clinical follow-up, as an objective morphological marker in therapeutic trials.

Amyotrophic Lateral Sclerosis↗

Functional imaging of parotid glands: diffusion-weighted echo-planar MRI before and after stimulation.

PURPOSE: To investigate the feasibility of diffusion-weighted (DW) echo-planar imaging (EPI) for measuring different functional conditions of the parotid gland and to compare different measurement approaches. MATERIALS AND METHODS: Parotid glands of 27 healthy volunteers were examined with a DW EPI sequence (TR 1,500 msec, TE 77 msec, field-of-view 250 x 250 mm, pixel size 2.10 x 1.95 mm, section thickness 5 mm) before and after oral stimulation with commercially available lemon juice. The b factors used were 0, 500, and 1,000 sec/mm (2). Apparent diffusion coefficient (ADC) maps were digitally transferred to MRIcro (Chris Rorden, University of Nottingham, Great Britain) and evaluated with a manually placed circular region of interest (ROI) containing 100 - 200 pixel. Additional ROIs including the entire parotid gland were placed on either side. The results of both measurements were compared, using the Student's t test based on the median ADC values for each person. A two-tailed p-value of less than.05 was determined to indicate statistical significance. To compare both measurement approaches, the Pearson's correlation coefficient (r) was calculated. RESULTS: Diffusion-weighted echo-planar MR imaging successfully visualized the parotid glands of all volunteers. In a first step, the median ADC value per person was computed. Using ROIs of 100 - 200 pixels, the mean was calculated to be 1.08 x 10 (- 3) mm (2)/sec +/- 0.12 x 10 (- 3) mm (2)/sec for both parotid glands prior to stimulation. After stimulation, the mean ADC was measured at 1.15 x 10 (- 3) mm (2)/sec +/- 0.11 x 10 (- 3) mm (2)/sec for both parotid glands. Evaluating the entire parotid gland, the ADC was 1.12 x 10 (- 3) mm (2)/sec +/- 0.08 x 10 (- 3) mm (2)/sec prior to stimulation, whereas the ADC increased to 1.18 x 10 (- 3) mm (2)/sec +/- 0.09 x 10 (- 3) mm (2)/sec after stimulation with lemon juice. For both types of measurements, the increase in ADC after stimulation proved to be significant (p < 0.001). High correlations between both measurement types were found (r >.83). CONCLUSION: Diffusion-weighted echo-planar MR imaging allows non-invasive quantification of functional changes in the parotid glands.

Adult↗

[Functional imaging of submandibular glands: diffusion-weighted echo-planar MRI before and after stimulation].

PURPOSE: To investigate the feasibility of diffusion-weighted (DWI) echo-planar imaging (EPI) to depict the submandibular glands and to measure different functional conditions. MATERIALS AND METHODS: Twenty-seven healthy volunteers were examined. Diffusion weighted sequence was performed prior to stimulation. Exactly 30 seconds after a commercially available lemon juice was given orally, the diffusion weighted sequence was repeated. All examinations were performed by using a 1.5-T superconducting system with a 30 mT/m maximum gradient capability and maximum slew rate of 125 mT/m/sec (Magnetom Symphony, Siemens, Erlangen, Germany). The lower part of the circularly polarized (CP) head coil and a standard two-element CP neck array coil were used. The flexibility of the neck array coil allowed positioning the N1 element (upper part of the coil) right next to the submandibular gland. The axial diffusion-weighted EPI (echo planar imaging) sequence was performed using a matrix of 119 x 128, a field of view of 250 x 250 mm (pixel size 2.1 x 1.95 mm), a section thickness of 5 mm with an interslice gap of 1 mm. The b factors used were 0 sec/mm(2), 500 sec/ mm(2) and 1000 sec/mm(2). Apparent diffusion coefficiant (ADC) maps were digitally transferred to MRIcro (Chris Rorden, Universitiy of Nottingham, Great Britain). After detecting the submandibular glands a region of interest (ROI) was placed manually exactly within the boarder of both submandibular glands, excluding the external carotid artery on ADC maps. These procedures were performed on all ADC slices the submandibular glands could be differentiated in before and after oral stimulation. For statistical comparison of results, a student's t-test was performed with an overall two-tailed significance level of p = 0.05. RESULTS: The visualization of the submandibular glands using the diffusion-weighted EPI sequence was possible in all of the 27 volunteers. Prior to oral stimulation an ADC of 1.31 x 10(-3) mm(2)/sec (95 % CI, 1.39 x 10(-3) mm(2)/sec, 1.44 x 10(-3) mm(2)/sec) was calculated which increased to 1.41 x 10(-3) mm(2)/sec (95 % KI, 1.39 x 10(- 3) mm(2)/sec, 1.44 x 10(-3) mm(2)/sec) 30 seconds after stimulation. This increase proved to be significant (p < 0.001). CONCLUSION: Diffusion-weighted echo-planar MR imaging allows non-invasive quantification of functional changes in the submandibular gland.

Adult↗

On the accuracy of noninvasive thermometry using molecular diffusion magnetic resonance imaging.

Temperature measurement using magnetic resonance imaging (MRI) of water self-diffusion is investigated. Diffusion images and derived temperatures are obtained in polyacrylamide gel phantom. The temperatures measured from MRI are compared with those from temperature probes to verify their accuracy. In general, the difference between temperatures determined from MRI diffusion images over 0.3 cm3 regions of interest and from temperature probes were 0.2 degrees C. It is concluded that current MRI technology allows noninvasive temperature tomography that is comparable with invasive thermometry with respect to temperature accuracy, has spatial and time resolutions that would be useful in hyperthermic oncology.

Body Temperature↗

New imaging strategies for patient selection for thrombolytic and neuroprotective therapies.

Ischemic stroke trials have traditionally sought to limit the range of disease studied according to several dimensions based on clinical examination and CT scan results. It has been proposed that the optimal sample for stroke trials would include a positive imaging diagnosis of a pathology rationally linked to the drug's mechanisms of action and that this would improve the likelihood of positive results. This principle has been supported by the results of the Prolyse in Acute Cerebral Thromoembolism II (PROACT II) study. Whereas trials of iv thrombolysis between 3 and 6 hours after symptom onset in a general sample of patients were not positive, selection of a subgroup by angiography was an effective strategy in this time period for PROACT II. This study contradicted the hypothesis that treatment of stroke beyond 3 hours would not be successful. MRI with diffusion and perfusion has been an appealing imaging modality because it provides pretreatment angiography, perfusion, and lesion volume information during a brief, non-invasive assessment. Current literature supports the validity of MRI as a marker for clinical severity and clinical improvement. The diffusion-perfusion mismatch, the MRI marker for the ischemic penumbra, is a very strong predictor of lesion volume growth. Several acute trials in progress use a positive imaging diagnosis for the basis of selection. As the field of stroke clinical trials examines opportunities for improving trial design, positive imaging diagnoses in patient selection are likely to assume an increasingly useful role.

Clinical Trials, Phase III as Topic↗

[Diffuse liver parenchymal diseases: the value of MRI compared to sonography and CT].

29 patients with diffuse liver disease were examined by ultrasound, CT and MRI. MRI imaging was performed using T1-and t2-weighted spin-echo-sequences and fast gradient-echo-sequences. The paramagnetic contrast agent Gd-DTPA was applied intravenously (0.1 mmol/kg). In all patients with hepatitis MRI enabled exact liver biopsy by delineation of inflammatory changes in cases of chronic or focal hepatitis. CT and ultrasound were superior to MRI in the detection of focal or diffuse fatty degeneration. However, MRI enabled an exact differentiation of fatty changes from neoplasm. In cases of fibrotic changes the most accurate findings could be shown by MRI. In patients suffering from hemochromatosis MRI supplied additional information compared to CT and ultrasound revealing significant reduction of signal intensity due to reinforced enhancement of iron. Concerning Wilson's disease MRI showed a characteristic pattern of parenchymal changes. The application of Gd-DTPA in cases of diffuse liver disease adds supplementary information about perfusion of liver parenchyma, but its value for diagnostic accuracy is only secondary.

Contrast Media↗

[The value of diffusion-weighted MRT in assessing the bone marrow changes in vertebral metastases].

AIM OF THE STUDY: The aim of the study was the evaluation of the diffusion coefficient (ADC) of vertebral metastasis and regular vertebral bodies with diffusion weighted MRI (DWI). DWI evaluates the tissue-specific molecular diffusion of protons. In tissues with high cell densities (neoplasm) a decreased ADC can be expected due to restricted diffusion according to an exaggerated amount of intra- and intercellular membranes (i.e. diffusion barriers). METHODS: In 5 breast cancer patients the ADC of both known vertebral metastases and of adjacent regular vertebral bodies were measured with DWI (1.0 T; Phased-Array-Body-Coil; b: 880 and 440 s/mm2). RESULTS: The ADC of regular vertebral bodies (1.3 +/- 0.23 x 10(-3) s/mm2) was significantly (p < or = 0.0002) higher than in vertebral metastases (0.39 +/- 0.11 x 10(-3) s/mm2). CONCLUSIONS: These data demonstrate that the ADC can be reliably measured in vertebral bodies. The quantitative evaluation of the ADC in vertebral bodies seems to be an objective and comparable parameter for differentiating malign from benign vertebral tissue.

Bone Marrow↗