Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients.

The purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and 18F-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (F D), SUVmax (F SUVmax) were statistically assessed. F D ≥ 1 and F ADC ≥ 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC ≥ 1 in both post-treatment scans and F D ≥ 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD40l, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.

The value of magnetic resonance spectroscopy as a supplement to MRI of the brain in a clinical setting.

BACKGROUND: There are different opinions of the clinical value of MRS of the brain. In selected materials MRS has demonstrated good results for characterisation of both neoplastic and non-neoplastic lesions. The aim of this study was to evaluate the supplemental value of MR spectroscopy (MRS) in a clinical setting. MATERIAL AND METHODS: MRI and MRS were re-evaluated in 208 cases with a clinically indicated MRS (cases with uncertain or insufficient information on MRI) and a confirmed diagnosis. Both single voxel spectroscopy (SVS) and chemical shift imaging (CSI) were performed in 105 cases, only SVS or CSI in 54 and 49 cases, respectively. Diagnoses were grouped into categories: non-neoplastic disease, low-grade tumour, and high-grade tumour. The clinical value of MRS was considered very beneficial if it provided the correct category or location when MRI did not, beneficial if it ruled out suspected diseases or was more specific than MRI, inconsequential if it provided the same level of information, or misleading if it provided less or incorrect information. RESULTS: There were 70 non-neoplastic lesions, 43 low-grade tumours, and 95 high-grade tumours. For MRI, the category was correct in 130 cases (62%), indeterminate in 39 cases (19%), and incorrect in 39 cases (19%). Supplemented with MRS, 134 cases (64%) were correct, 23 cases (11%) indeterminate, and 51 (25%) incorrect. Additional information from MRS was beneficial or very beneficial in 31 cases (15%) and misleading in 36 cases (17%). CONCLUSION: In most cases MRS did not add to the diagnostic value of MRI. In selected cases, MRS may be a valuable supplement to MRI.

Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging.

PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content. RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265). CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1232-1240.

MR spectroscopy of the prostate at 3T: measurements of relaxation times and quantification of prostate metabolites using water as an internal reference.

PURPOSE: We performed single-voxel magnetic resonance spectroscopy (MRS) of the human prostate at 3 tesla using a surface coil to measure prostate water, choline (Cho), creatine (Cr), and citrate (Cit) relaxation times T1, T2, and to estimate concentrations of Cho, Cr, and Cit in healthy volunteers. METHODS: In nine of 17 healthy volunteers, we performed experiments to estimate relaxation time, and we used the spectra of the other eight to compute metabolite concentrations. Spectra were processed by LCModel and AMARES (advanced method for accurate, robust, and efficient spectral fitting) algorithms. T1 and T2 values were obtained by monoexponential fitting of the spectral intensities. Metabolite concentrations were estimated using prostate tissue water as an internal concentration reference. RESULTS: Relaxation times are reported for prostate water (T1, 2163±166 ms; T2, 110±18 ms), Cho (T1, 987±71 ms; T2, 239±24 ms), Cr (T1, 1128±149 ms; T2, 188±20 ms), and Cit (T1, 476±70 ms; T2, 228±42 ms). Mean concentrations in healthy prostate were Cho, 2.6±0.3 mM, Cr, 5.8±1.3 mM, and Cit, 26.9±5.5 mM. CONCLUSION: We observed metabolite relaxation times and concentrations consistent with published values of healthy volunteers at 1.5 and 3T. T1 values increased and T2 slightly decreased with magnetic field strength. Our preliminary patient results indicate that water-referenced quantitative MRS of the human prostate is a promising tool for monitoring therapeutic effects and detecting tumor relapse, i.e., in situations when Cit intensity is small or undetectable.

MR spectroscopy of the human prostate using surface coil at 3 T: metabolite ratios, age-dependent effects, and diagnostic possibilities.

PURPOSE: To measure prostate spectra of healthy volunteers using a surface coil, to demonstrate age-dependent effects, and to investigate diagnostic possibilities for prostate cancer detection. MATERIALS AND METHODS: Single-voxel and 2D magnetic resonance spectroscopic imaging (MRSI) spectra of 51 healthy volunteers with biopsy-proven prostate carcinoma of 20 patients for comparison were measured and processed using the LCModel. The mean normalized spectra and mean metabolite-to-citrate intensity ratios were computed. RESULTS: Metabolite-to-citrate ratios of healthy volunteers were lower in the older group (>51 years) than in the younger group (<45 years). The peripheral zone (PZ) revealed a lower metabolite-to-citrate intensity ratio than the central gland (CG). Age-related differences in metabolite-to-citrate ratio were insignificant in the voxels with predominantly CG tissue, whereas significant differences were found in the PZ. Sensitivity in detecting prostate cancer by single-voxel spectroscopy (SVS) and 2D MRSI was 75% and 80%, respectively. CONCLUSION: SVS and 2D MRSI of the prostate at 3 T, using a surface coil, are useful in situations when insertion of the endorectal coil into the rectum is difficult or impossible. Our findings of age-dependent effects may be of importance for the analysis of patient spectra.

Quantification of lipids in human lower limbs using yellow bone marrow as the internal reference: gender-related effects.

The main purpose of this study was to determine and compare extra- and intramyocellular (IMCL) lipids content in the calf and thigh muscles of normal male and female volunteers using high-spatial-resolution magnetic resonance spectroscopic imaging (MRSI). The study groups consisted of 10 females and 10 males. The subjects were healthy and normal-weight. Fat (yellow bone marrow) was used as the internal concentration reference. Total fat and IMCL content were computed for all muscles in the slice and for three muscle compartments in the thigh, whereas three muscles and three muscle compartments were evaluated in the calf. To avoid the confounding effects of physical activity and diet, measurements were performed in the same session. A common feature for both genders was that thigh muscles had approximately 2.5 times greater total fat content as compared to muscles of the calf. The mean IMCL level was, however, more than 3 times higher in the calf muscles compared with the thigh. No significant differences in lipid concentrations of correspondent regions of interest were found between genders. The high-spatial-resolution MRSI technique enables a more detailed study of muscle lipid distribution and can therefore improve understanding of muscle lipid metabolism in healthy volunteers and in studies of patients with metabolic disorders.

Short echo time MR spectroscopy of brain tumors: grading of cerebral gliomas by correlation analysis of normalized spectral amplitudes.

PURPOSE: To process single voxel spectra of low- and high-grade gliomas. To propose correlation analysis of the scatter plots of normalized spectral amplitudes as a pattern recognition tool for the classification (grading) of brain tumors. To propose a spectrum processing approach that improves the differentiation of proton spectra with dominating macromolecule and lipid peaks. MATERIALS AND METHODS: LCModel was used to process spectra. Mean metabolite concentrations and mean normalized spectra were obtained for normal white matter and for gliomas. The mean spectra of macromolecules and lipids (ML) in the range 1.4-0.9 ppm, and mean difference spectra (DS) without ML and lactate were computed. Correlation analysis of the scatter plot of the patient and mean normalized spectral amplitudes and dispersion of the scatter plot points were used for classification and grading of tumors. RESULTS: It was found advantageous to perform the classifications using DS spectra. The shape of ML spectrum and concentration of tCr seem to be a good markers for glioma grade. CONCLUSION: Combining a qualitative comparison of the patient and mean DS spectra of the tumors using correlation analysis of normalized spectra amplitudes with a quantitative comparison of metabolite concentrations is a powerful tool in studying brain lesions.

Two-dimensional spectroscopic imaging for pretreatment evaluation of prostate cancer: comparison with the step-section histology after radical prostatectomy.

PURPOSE: To minimize user and vendor dependence of the spectrum processing of prostate spectra, to measure the ratio of choline (Cho) plus creatine (Cr) to citrate (Cit) in the prostate tissue of normal volunteers and cancer patients, and to compare the results with pathologic findings after radical prostatectomy. MATERIALS AND METHODS: Four healthy volunteers and 13 patients with prostate cancer were measured. Measurements were performed using two-dimensional magnetic resonance spectroscopic imaging (MRSI) and endorectal coil. A standard vendor's spectrum processing approach has been modified. An original feature of this methodology was the combination of vendor-optimized and user-independent spectrum preprocessing in the scanner and user-independent quantitation in the environment of an MRUI software package. (Cho+Cr)/Cit ratio was used for the classification of prostate tissue. Results were compared with histopathology after radical prostatectomy. RESULTS: Eight of 13 cancer patients were classified as suspicious or very suspicious for cancer at spectroscopy, three were ambiguous for cancer and two patients were evaluated as false negative. A considerable overlap of metabolite ratios at various Gleason score was found. CONCLUSION: The proposed spectrum processing has the potential to improve the accuracy and user independency of the (Cho+Cr)/Cit quantitation. This study confirmed the previous results that a considerable overlap of (Cho+Cr)/Cit ratios exists at various Gleason score levels.