Does arterial spin-labeling MR imaging-measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model?

PURPOSE: To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic therapy can predict later resistance to therapy. MATERIALS AND METHODS: Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma (RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498 (3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences. RESULTS: Baseline blood flow was 80.1 mL/100 g/min +/- 23.3 (standard deviation) for A498, 75.1 mL/100 g/min +/- 28.6 for 786-0, and 10.2 mL/100 g/min +/- 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min +/- 7.6) in flow, whereas flow decreased in all treated A498 on day 14 (47.9 mL/100 g/min +/- 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min +/- 8.7) (P = .003 and .03, respectively). For A498, lowest values were measured at 28-42 days of receiving sorafenib. Regions of increased flow occurred on days 35-49, 17-32 days before documented tumor growth and before significant increases in mean flow (day 77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent days (P > .99). CONCLUSION: ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib.

An assessment of the sharpness of carotid artery tissue boundaries with acquisition voxel size and field strength.

A measure of the sharpness of vessel wall interfaces in carotid artery MRI may be useful for assessing the conspicuity of the wall's features. An edge detection technique was used to measure the signal intensity gradients in 2D time-of-flight (2D-TOF) and double-inversion recovery black-blood (DIR-BB) carotid artery images of normal subjects that were acquired at 1.5 T with 0.55 x 0.55 x 2.0-mm (0.6 mm3) acquisition voxels and zero filled to reduce the in-plane reconstructed voxel size by one half in each dimension as well as with 0.27 x 0.27 x 2.0-mm (0.15 mm3) acquisition voxels and at 3.0 T with 0.27 x 0.27 x 2.0-mm (0.15 mm3) acquisition voxels using surface coils. The gradient intensities of the lumen-to-background interface varied closely with the contrast-to-noise ratio of the 2D-TOF imaging. For the DIR-BB imaging, in which higher spatial frequency artery structures are visible, the gradient intensities at the interfaces were higher than theoretically predicted at both field strengths with smaller acquisition voxels. The use of acquisition voxels smaller than those previously used at 1.5 T can improve the visualization of carotid artery structures at 1.5 and 3.0 T with surface coil reception.

3T MR of the prostate: reducing susceptibility gradients by inflating the endorectal coil with a barium sulfate suspension.

Most prostate MRI/MRS examinations are performed with an endorectal coil inflated with air, leading to an air-tissue interface that induces magnetic susceptibility gradients within the gland. Inflation of the coil with a barium sulfate suspension is described and compared to inflation with air or liquid perfluorocarbon (PFC). The B(0) field in the prostate gland was mapped for five healthy volunteers when the endorectal coil was inflated with each of the three agents. A marked decrease in the posterior-anterior (P-A) field gradient and a significant improvement in field homogeneity were evident in the presence of a barium suspension and PFC relative to air. MRS data acquired from the prostate gland in the presence of air, PFC, and a barium suspension in the endorectal coil showed similar trends, demonstrating improvement in line-widths and spectral resolution when the barium suspension or the PFC were inflating the endorectal coil. On this basis we conclude that a barium suspension provides an available, cheap, and safe alternative to PFC, and we suggest that inflating the endorectal coil with a barium suspension should be considered for prostate MR studies, especially at high field strengths (such as 3T).

Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity.

OBJECTIVE: The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation. RESEARCH DESIGN AND METHODS: CBF was examined in 26 diabetic (aged 61.6 +/- 6.6 years) and 25 control (aged 60.4 +/- 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla. RESULTS: The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (-13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (-3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region. CONCLUSIONS: Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.

Limits on activation-induced temperature and metabolic changes in the human primary visual cortex.

Changes in cerebral blood flow (CBF) and metabolism are now widely used to map and quantify neural activity, although the underlying mechanism for these changes is still incompletely understood. Magnetic resonance spectroscopy (MRS) at 3T, synchronized with a 32-s block design visual stimulation paradigm, was employed to investigate activation-induced changes in temperature and metabolism in the human primary visual cortex. A marginally significant increase in the local temperature of the visual cortex was found (0.1 degrees C, P = 0.09), excluding the possibility of a temperature decrease (95% confidence interval (CI) = 0.0-0.2 degrees C), which was previously suggested. A comparison with models of thermal equilibrium in the presence of blood flow suggests that an increase in heat production during activation, greater than or at least equal to that produced by the complete oxidative metabolism of the elevated glucose (Glc) utilization accompanying activation, would be required to offset the cooling effects of the increased blood flow. The total pools of glutamate (Glu), glutamine (Gln), myo-Inositol (mI), N-acetylaspartate (NAA), choline (Cho), and lactate (Lac) were not significantly affected by activation. Limits on Lac concentration changes were too weak to constrain theories of the metabolic use of elevated Glc consumption during stimulation, and emphasize the challenges of measuring even large Lac changes accompanying stimulation.

Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy.

Increased utilization of cross-sectional imaging has resulted in increased detection of incidental renal tumors. The noninvasive characterization of renal tissue has important implications for the diagnosis of renal malignancies and treatment monitoring. Recently, multiple breath-hold averaged proton magnetic resonance spectroscopy ((1)H-MRS) performed at high field has enabled the use of this noninvasive metabolic profiling technique for the investigation of the abdomen. Multiple breath-hold averaged (1)H-MRS at high field (3T) was obtained in the kidneys of 10 healthy volunteers and in renal cell carcinoma tumors of 14 patients. The spectra of normal kidneys showed four main groups of resonances: 1) at 5.4-5.6 ppm, attributed to C6 of cholesterol and the unsaturated parts of the olefinic region of fatty acids; 2) at 4.7 ppm, attributed to the residual water signal; 3) at 3.2 ppm, attributed to trimethylamine moiety of choline metabolites; and 4) at 1.3 and 0.9 ppm, attributed to the methylenes and terminal methyls of lipids. The ratio of the signal at 5.4 ppm to that of 1.3 ppm was 19-fold lower in renal cell carcinomas than in healthy kidneys, tied P = 0.0003 Mann-Whitney U-test, suggesting a decrease in both free cholesterol and the degree of unsaturation of fatty acids in the malignant tissue. This metabolic shift is in agreement with previous ex vivo studies of human renal cell carcinoma. The ability to detect renal metabolic shifts noninvasively may improve the specificity of preoperative renal tissue characterization and may provide a new modality for treatment monitoring.

3 Tesla magnetic resonance imaging of the prostate with combined pelvic phased-array and endorectal coils; Initial experience(1).

RATIONALE AND OBJECTIVES: High-resolution magnetic resonance imaging of the prostate at 1.5T has gained acceptance for pretherapeutic staging of prostate cancer. The aim of this study was to evaluate the potential clinical utility of combined pelvic phased-array and endorectal coils at 3T. MATERIALS AND METHODS: Six volunteers were examined on 1.5T and 3T scanners with pelvic phased-array surface coil combined with a disposable endorectal prostate coil. RESULTS: We were able to acquire T2-W fast spin echo images with 1.5 mm slices, field of view 12, matrix 320 x 192, (voxel size 0.35 mm(3)), with excellent anatomic detail and good T2 contrast. A 1.5 mm axial slice thickness permitted high-quality multiplanar reconstructions with clear visualization of small patho-anatomic structures. Dynamic contrast-enhanced gradient echo images showed excellent spatial resolution (voxel size, 0.38 mm(3)) and temporal resolution. With this level of anatomic information in dynamic images we could clearly distinguish between intracapsular and extracapsular contrast enhancement. CONCLUSION: Using modified T2-fast spin echo and dynamic contrast-enhanced gradient echo sequences, we obtained whole gland coverage with 35-38 microm(3) resolution, without interfering artifacts, in reasonable acquisition times and staying well below the specific absorption rate guidelines. The high spatial resolution in the axial plane allowed meaningful multiplanar reconstructions. The initial results show the clinical utility of endorectal 3T for the noninvasive evaluation of the prostate with image features and quality not achievable at 1.5 T.