Susan M. Noworolski

An automated technique for the quantitative assessment of 3D-MRSI data from patients with glioma.

Although proton magnetic resonance spectroscopic imaging (1H‐MRSI) has been shown to be effective for localizing tumor in patients with gliomas, it is not a routinely used clinical tool. This is due, in part, to the lack of a standardized, objective method for analyzing spectra. We present an automated technique for a) selecting a population of voxels from each patient that have the spectral features of normal brain regions, and b) using the selected voxels as internal controls for quantifying the probability of abnormality at each voxel location. The technique was demonstrated on a phantom, 14 normal volunteers, and 30 patients with histologically proven tumor. In addition, we demonstrated the usefulness of the method for monitoring patients in serial studies from two glioma patients with progressive disease. J. Magn. Reson. Imaging 2001;13:167–177.

Dynamic contrast-enhanced MRI in normal and abnormal prostate tissues as defined by biopsy, MRI, and 3D MRSI.

This study characterized dynamic contrast‐enhanced (DCE) MRI of prostate tissues: cancerous peripheral zone (PZ), normal PZ, stromal benign prostatic hyperplasia (BPH), and glandular BPH. MRI, MRSI, and DCE MRI were performed on 25 patients. Tissues were identified with MRI, MRSI, and (when available) biopsy results. Motion between MRI and DCE MRI, and within DCE MRI was assessed and manually corrected. To assess tissue and patient effects, native T1s were measured in 12 of 25 patients, and DCE MRI results were normalized to muscle enhancement. Regions of cancer had a higher peak enhancement (P < 0.006), faster enhancement rate (P < 0.0008), and faster washout slope (P < 0.05) than normal PZ tissues. Stromal BPH had the fastest enhancement rate (P < 0.003) of all tissues and tended to have the greatest enhancement. Intersequence motion averaged 2.6 mm and reached 7.9 mm. Motion within DCE MRI was generally minimal (<2 pixels), but one case showed a large shift that would have confounded the results. Native T1s were similar across the prostatic tissues. Interpatient variability in DCE MRI was only partially reduced by normalization to muscle. DCE MRI of the prostate discriminated PZ cancer from normal PZ tissues and predominantly stromal and glandular BPH. Magn Reson Med 53:249–255, 2005.

Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging

Combined MRI and 3D spectroscopic imaging (MRI/3D‐MRSI) was used to study the metabolic effects of hormone‐deprivation therapy in 65 prostate cancer patients, who underwent either short, intermediate, or long‐term therapy, compared to 30 untreated control patients. There was a significant time‐dependent loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormone‐deprivation therapy, resulting in the complete loss of all observable metabolites (total metabolic atrophy) in 25% of patients on long‐term therapy. The amount and time‐course of metabolite loss during therapy significantly differed for healthy and malignant tissues. Citrate levels decreased faster than choline and creatine levels during therapy, resulting in an increase in the mean (choline + creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI detectable citrate, this ratio could not be used to identify cancer in 69% of patients on long‐term therapy. In the absence of citrate, however, residual prostate cancer could still be detected by elevated choline levels (choline/creatine ratio ≥1.5), or the presence of only choline in the proton spectrum. The loss of citrate and the presence of total metabolic atrophy correlated roughly with decreasing serum prostatic specific antigen levels with increasing therapy. In summary, MRI/3D‐MRSI provided both a measure of residual cancer and a time‐course of metabolic response following hormone‐deprivation therapy. Magn Reson Med 46:49–57, 2001.

Magnetic resonance imaging for secondary assessment of breast density in a high-risk cohort

A quantitative measure of three-dimensional breast density derived from noncontrast magnetic resonance imaging (MRI) was investigated in 35 women at high-risk for breast cancer. A semiautomatic segmentation tool was used to quantify the total volume of the breast and to separate volumes of fibroglandular and adipose tissue in noncontrast MRI data. The MRI density measure was defined as the ratio of breast fibroglandular volume over total volume of the breast. The overall correlation between MRI and mammographic density measures was R(2)=.67. However the MRI/mammography density correlation was higher in patients with lower breast density (R(2)=.73) than in patients with higher breast density (R(2)=.26). Women with mammographic density higher than 25% exhibited very different magnetic resonance density measures spread over a broad range of values. These results suggest that MRI may provide a volumetric measure more representative of breast composition than mammography, particularly in groups of women with dense breasts. Magnetic resonance imaging density could potentially be quantified and used for a better assessment of breast cancer risk in these populations.

Dynamic contrast-enhanced MRI and MR diffusion imaging to distinguish between glandular and stromal prostatic tissues.

PURPOSE To compare peak enhancement (PE), determined from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and the magnetic resonance (MR) directionally-averaged apparent diffusion coefficient () in glandular versus stromal prostatic tissues and, with this comparison, to infer if the hypothesis that gadolinium-DTPA (Gd-DTPA) does not enter healthy glands or ducts is plausible. MATERIALS AND METHODS MRI, MR spectroscopic imaging, DCE MRI and MR diffusion were evaluated in 17 untreated subjects with suspected or proven prostate cancer. PE and were compared in glandular-ductal tissues [normal peripheral zone and glandular benign prostatic hyperplasia (BPH)] and stromal-low ductal tissues (central gland/mixed BPH and stromal BPH). RESULTS The glandular-ductal tissues had lower PE [125+/-6.4 (% baseline)] and higher [1.57+/-0.15 (s/10(-3) mm2)] than the stromal-low ductal tissues [PE=132+/-5.5 (% baseline) (P< .0008), =1.18+/-0.20 (s/10(-3) mm2) (P< 1 x 10(-8))]. A statistical model based upon stepwise regression was generated and completely separated the tissue types: ductal Measure = 448+669 x (s/10(-3) mm2)-10.7 x PE (1/%), R2=1.0 and P<8 x 10(-10). CONCLUSIONS The very different MR results in the glandular-ductal versus stromal-low ductal tissues suggest that these tissues have different underlying structure. These results support the hypothesis that Gd-DTPA does not enter healthy prostatic glands or ducts. This may explain the higher PE and lower that previously have been reported in prostate cancer versus healthy tissue.

Registration of MR prostate images with biomechanical modeling and nonlinear parameter estimation

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) have been shown to be very useful for identifying prostate cancers. For high sensitivity, the MRI/MRSI examination is often acquired with an endorectal probe that may cause a substantial deformation of the prostate and surrounding soft tissues. Such a probe is removed prior to radiation therapy treatment. To register diagnostic probe-in magnetic resonance (MR) images to therapeutic probe-out MR images for treatment planning, a new deformable image registration method is developed based on biomechanical modeling of soft tissues and estimation of uncertain tissue parameters using nonlinear optimization. Given two-dimensional (2-D) segmented probe-in and probe-out images, a finite element method (FEM) is used to estimate the deformation of the prostate and surrounding tissues due to displacements and forces resulting from the endorectal probe. Since FEM requires tissue stiffness properties and external force values as input, the method estimates uncertain parameters using nonlinear local optimization. The registration method is evaluated using images from five balloon and five rigid endorectal probe patient cases. It requires on average 37 s of computation time on a 1.6 GHz Pentium-M PC. Comparing the prostate outline in deformed probe-out images to corresponding probe-in images, the method obtains a mean Dice Similarity Coefficient (DSC) of 97.5% for the balloon probe cases and 98.1% for the rigid probe cases. The method improves significantly over previous methods (P < 0.05) with greater improvement for balloon probe cases with larger tissue deformations.

High spatial resolution 1H-MRSI and segmented MRI of cortical gray matter and subcortical white matter in three regions of the human brain

High‐resolution MR imaging and spectroscopic imaging were used to study differences in proton spectra between cortical gray matter and subcortical white matter in 23 normal volunteers using a 1.5 T scanner and surface coil receivers. A point‐resolved spectroscopy (PRESS) volume with an 8 × 8 × 8 phase‐encoding matrix was used to acquire over 1900 0.09–0.2 cc spectral voxels. The high‐resolution (0.7 × 0.7 × 0.8 mm3 or 0.8 × 0.8 × 1 mm3) images were corrected for the surface coil reception profile and segmented into cerebrospinal fluid (CSF) and gray and white matter to correlate with the spectra. The data showed that N‐acetyl aspartate (NAA) and creatine (Cr) were higher in the gray matter than in the white matter (NAAg/w = 1.4 ± 0.36, Crg/w = 1.4 ± 0.41). Choline was significantly lower in the gray matter of the occipital lobe than in the white matter (0.73 ± 0.19), but not significantly different in the other regions. NAA/Cho was found to be significantly higher in the occipital lobe than in the left frontal or vertex regions. Magn Reson Med 41:21‐29, 1999.

Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat

CONTEXT Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain. OBJECTIVES We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose. DESIGN, SETTING, AND PARTICIPANTS Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy. RESULTS Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 ± 1.4% vs 11.0 ± 1.4% for CCHO; P = .001) and higher liver fat (median, +137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP. CONCLUSION Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome.

Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n = 27) and African‐American (n = 16) children with obesity and metabolic syndrome.

Liver steatosis: investigation of opposed-phase T1-weighted liver mr signal intensity loss and visceral fat measurement as biomarkers

PURPOSE To investigate if opposed-phase T1-weighted and fat-suppressed T2-weighted liver signal intensity (SI) loss and visceral fat measurement at magnetic resonance (MR) imaging and body mass index (BMI) are correlated with grade of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-related liver disease. MATERIALS AND METHODS Committee on Human Research approval and patient consent were obtained for this HIPAA-compliant study. Fifty-two patients (15 men, 37 women) with NAFLD (n = 29) or HCV and HIV-related liver disease (n = 23) underwent prospective contemporaneous MR imaging and liver biopsy. Liver SI loss was measured on opposed-phase T1-weighted and fat-suppressed T2-weighted MR images. Visceral fat area was measured at three levels on water-suppressed T1-weighted MR images (n = 44). Spearman rank correlation coefficients and recursive partitioning were used to examine correlations. RESULTS Histopathologic liver steatosis correlated well with liver SI loss on opposed-phase T1-weighted MR images (rho = 0.78), fat-suppressed T2-weighted MR images (rho = 0.75), and average visceral fat area (rho = 0.77) (all P < .01) but poorly with BMI (rho = 0.53, P < .01). Liver SI losses on opposed-phase T1-weighted MR imaging of less than 3%, at least 3% but less than 35%, at least 35% but less than 49%, and at least 49% corresponded to histopathologic steatosis grades of 0 (n = 16 of 17), 1 (n = 11 of 16), 2 (n = 7 of 13), and 3 (n = 5 of 6), respectively. A visceral fat area of greater than or equal to 73.8 cm(2) was associated with the presence of histopathologic steatosis in 41 of 44 patients. CONCLUSION Liver SI loss on opposed-phase T1-weighted MR images and visceral fat area may be used as biomarkers for the presence of liver steatosis and appear to be superior to BMI.