Hypoenhancing prostate cancers on dynamic contrast-enhanced MRI are associated with poor outcomes in high-risk patients: results of a hypothesis generating study.

PURPOSE: To investigate the association of hypoenhancement on dynamic Contrast enhanced (DCE) with prostate cancer patient outcomes. MATERIAL AND METHODS: This was a single-institution retrospective Institutional Review Board (IRB)-approved cohort study of 54 men who had prostate Magnetic Resonance Imaging (MRI) within 6 months of cancer diagnosis between 01/2012 to 03/2014. Two readers independently identified the dominant MRI-lesions utilizing Prostate Imaging-Reporting and Data System-version2- guidelines. These lesions were classified as hypoenhancing or hyperenhancing, compared to normal peripheral zone using quantitative DCE analysis. The t test for unequal sample sizes and the two-sample Wilcoxon rank-sum tests were used to compare groups. Logistic regression determined if DCE characteristics predict the development of metastases or prostate cancer death. RESULTS: Time-to-progression was significantly shorter for hypoenhancing tumors (6.2 vs. 24.8 months, p = 0.05). Men with these lesions had a higher odds of having poor outcome (univariate logistic regression, odds ratio (OR) 6.79, 95% confidence interval (CI) 1.45-31.72, p = 0.02; multivariate analysis, OR 2.05, 95% CI 0.30-13.72, p = 0.47). Hypoenhancing tumors were larger (33.1 vs. 19.1 mm, p < 0.001) and more likely to be intermediate (Gleason scores 3 + 4 and 4 + 3) and high-grade (Gleason scores ≥ 4 + 4) prostate cancers (p = 0.05). Men in the hypoenhancing group had a higher mean prostate-specific antigen (PSA) value (87.6 vs. 24.8 ng/dL, p = 0.01) and PSA density (1.54 vs. 0.72, p = 0.03). The mean Ktrans and kep of hypoenhancing lesion were lower when compared to hyperenhancing lesions (p = 0.03 and p = 0.04). Ve values did not differ (p = 0.25). CONCLUSION: Men with hypoenhancing prostate cancers may have a worse prognosis than men with hyperenhancing tumors.

Estimation of metabolite T1 relaxation times using tissue specific analysis, signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data.

OBJECT: A novel method of estimating metabolite T1 relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T1 estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T1 by taking advantage of the spatial distribution information provided by MRSI. MATERIAL AND METHODS: The method, validated by Monte Carlo studies, involves a voxel averaging to preserve the GM/WM distribution, a non-linear least squares fit of the metabolite T1 and an estimation of its standard error by bootstrapping. It was applied in vivo to estimate the T1 of N-acetyl compounds (NAA), choline, creatine and myo-inositol in eight normal volunteers, at 1.5 T, using a short echo time 2D-MRSI slice located above the ventricles. RESULTS: WM-T 1,NAA was significantly (P < 0.05) longer in anterior regions compared to posterior regions of the brain. The anterior region showed a trend of a longer WM T1 compared to GM for NAA, creatine and myo-Inositol. Lastly, accounting for the bootstrapped standard error estimate in a group mean T1 calculation yielded a more accurate T1 estimation. CONCLUSION: The method successfully measured in vivo metabolite T1 using MRSI and can now be applied to diseased brain.

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 T1's 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 T1's 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.

Three-dimensional proton MR spectroscopic imaging of premature and term neonates.

BACKGROUND AND PURPOSE: Previous studies have primarily used single-voxel techniques to obtain MR spectra from the neonatal brain. In this study, we applied 3D MR spectroscopic imaging techniques to detect the spatial distribution of MR spectroscopic imaging-detectable compounds in premature and term infants. The goals were to test the feasibility of obtaining 3D MR spectroscopic images of newborns, assess the spatial variations of metabolite levels, and determine age-dependent differences in MR spectroscopic imaging data. METHODS: MR spectroscopic imaging data were acquired from nine premature (postconceptional age, 30-34 weeks) and eight term (postconceptional age, 38-42 weeks) neonates, all with normal clinical and neurologic outcomes. A specialized point-resolved spectroscopy sequence with very selective saturation pulses was used to select a region encompassing the majority of the brain. Phase encoding in three dimensions was performed in a 17-minute acquisition time to obtain 3D spectral arrays with a 1.0 cm(3) nominal spatial resolution. RESULTS: This study showed the feasibility of detecting the 3D distributions of choline, creatine, and N-acetylaspartate resonances in the neonatal brain. Significant spectral differences were detected among anatomic locations and between the premature and term groups. CONCLUSION: This initial study indicates that 3D MR spectroscopic imaging of the neonatal brain can detect anatomic and age-dependent variations in metabolite levels. This technique seems to be a powerful tool to assess the metabolic differences between anatomic regions and to follow the changes in cellular metabolites with brain maturation. This study also indicates the need for determining topologic and age-matched normative values before metabolic abnormalities in neonates can be accurately assessed by MR spectroscopy.

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 > or =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.

Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens.

BACKGROUND AND PURPOSE: Tumor progression is often difficult to distinguish from nonneoplastic treatment response on the basis of MR images alone. This study correlates metabolite levels measured by preoperative MR spectroscopic (MRS) imaging with histologic findings of biopsies, obtained during image-guided resections of brain mass lesions, to clarify the potential role of MRS in making this distinction. METHODS: Twenty-nine patients with brain tumors underwent high-resolution (0.2-1 cc) 3D proton MRS imaging and MR imaging before undergoing surgery; 11 had a newly diagnosed neoplasm, and 18 had recurrent disease. Surgical biopsies were obtained from locations referenced on MR images by guidance with a surgical navigation system. MR spectral voxels were retrospectively centered on each of 79 biopsy locations, and metabolite levels were correlated with histologic examination of each specimen. RESULTS: All mass lesions studied, whether attributable to tumor or noncancerous effects of previous therapy, showed abnormal MR spectra compared with normal parenchyma. When the pattern of MRS metabolites consisted of abnormally increased choline and decreased N-acetyl aspartate (NAA) resonances, histologic findings of the biopsy specimen invariably was positive for tumor. When choline and NAA resonances were below the normal range, histologic findings were variable, ranging from radiation necrosis, astrogliosis, and macrophage infiltration to mixed tissues that contained some low-, intermediate-, and high-grade tumor. CONCLUSION: This study demonstrated that 3D MRS imaging can identify regions of viable cancer, which may be valuable for guiding surgical biopsies and focal therapy. Regions manifesting abnormal MR spectra had a mixture of histologic findings, including astrogliosis, necrosis, and neoplasm.

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors.

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.

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.

Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas.

BACKGROUND AND PURPOSE: Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role of rCBV in the determination of recurrent/residual disease in patients with treated gliomas. METHODS: Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions. RESULTS: In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively. CONCLUSION: This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.

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 x 8 x 8 phase-encoding matrix was used to acquire over 1900 0.09-0.2 cc spectral voxels. The high-resolution (0.7 x 0.7 x 0.8 mm3 or 0.8 x 0.8 x 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 (NAA(g/w) = 1.4+/-0.36, Cr(g/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.

Serial proton magnetic resonance spectroscopy imaging of glioblastoma multiforme after brachytherapy.

The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.