[Show abstract][Hide abstract] ABSTRACT: The impact of high-resolution magic angle spinning (HR-MAS) spectroscopy on the histopathologic and mRNA integrity of human prostate tissues was evaluated. Forty prostate tissues were harvested at transrectal ultrasound (TRUS) guided biopsy (n = 20) or radical prostatectomy surgery (n = 20), snap-frozen on dry ice, and stored at -80°C until use. Twenty-one samples (n = 11 biopsy, n = 10 surgical) underwent HR-MAS spectroscopy prior to histopathologic and cDNA microarray analysis, while 19 control samples (n = 9 biopsy, n = 10 surgical) underwent only histopathologic and microarray analysis. Frozen tissues were sectioned at 14-µm intervals and placed on individual histopathology slides. Every 8th slide was stained with hematoxylin and eosin (H&E) and used to target areas of predominantly epithelial tissue on the remaining slides for mRNA integrity and cDNA microarray analysis. Histopathologic integrity was graded from 1 (best) to 5 (worst) by two 'blinded' pathologists. Histopathologic integrity scores were not significantly different for post-surgical tissues (HR-MAS vs controls); however, one pathologist's scores were significantly lower for biopsy tissues following HR-MAS while the other pathologist's scores were not. mRNA integrity assays were performed using an Agilent 2100 Bioanalyzer and the electrophoretic traces were scored with an RNA integrity number (RIN) from 1 (degraded) to 10 (intact). RIN scores were not significantly different for surgical tissues, but were significantly lower for biopsy tissues following HR-MAS spectroscopy. The isolated mRNA then underwent two rounds of amplification, conversion to cDNA, coupling to Cy3 and Cy5 dyes, microarray hybridization, imaging, and analysis. Significance analysis of microarrays (SAM) identified no significantly over- or under-expressed genes, including 14 housekeeping genes, between HR-MAS and control samples of surgical and biopsy tissues (5% false discovery rate). This study demonstrates that histopathologic and genetic microarray analysis can be successfully performed on prostate surgical and biopsy tissues following HR-MAS analysis; however, biopsy tissues are more fragile than surgical tissues.
NMR in Biomedicine 05/2010; 23(4):391-8. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to develop a reliable model for the calculation of gestational age (GA) in second and third trimesters with the use of amniotic fluid (AF) metabolite profiles that were determined by magnetic resonance spectroscopy.
High-resolution (11.7 T) ex vivo magnetic resonance spectroscopy was performed on 95 AF samples (mean, 31.7 weeks; range, 15.6-39.9 weeks). GA was determined by last menstrual period or first-trimester ultrasound scanning. Concentrations of 21 AF metabolites were measured with automated techniques. Metabolite concentrations, inverses, natural logs, and squares were entered as predictive variables in a stepwise linear regression model.
The following formula was derived: GA = 64.922 - (14.456 x alanine) + (4.965 x natural log [creatinine]) - (0.931 x glucose) - (5.202 x valine). This model fit the data with an R(2) value of 0.926. Average error among all samples was +/-1.75 weeks (SD, +/-1.43 weeks), for the second trimester was +/-2.21 weeks (SD, +/-1.78 weeks), and for the third trimester was +/-1.59 weeks (SD, +/-1.26 weeks).
Statistical modeling accurately predicted GA with amniotic fluid metabolite profiles that were obtained by magnetic resonance spectroscopy, which may represent a significant improvement over conventional ultrasound dating in the third trimester. Future studies should compare these techniques directly.
American journal of obstetrics and gynecology 04/2010; 203(1):76.e1-76.e10. · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish and compare normative metabolite concentrations in 2nd and 3rd trimester human amniotic fluid samples in an effort to reveal metabolic biomarkers of fetal health and development.
Twenty-one metabolite concentrations were compared between 2nd (15-27 weeks gestation, N = 23) and 3rd (29-39 weeks gestation, N = 27) trimester amniotic fluid samples using (1)H high resolution magic angle spinning (HR-MAS) spectroscopy. Data were acquired using the electronic reference to access in vivo concentrations method and quantified using a modified semi-parametric quantum estimation algorithm modified for high-resolution ex vivo data.
Sixteen of 21 metabolite concentrations differed significantly between 2nd and 3rd trimester groups. Betaine (0.00846+/-0.00206 mmol/kg vs. 0.0133+/-0.0058 mmol/kg, P < 0.002) and creatinine (0.0124+/-0.0058 mmol/kg vs. 0.247+/-0.011 mmol/kg, P < 0.001) concentrations increased significantly, while glucose (5.96+/-1.66 mmol/kg vs. 2.41+/-1.69 mmol/kg, P < 0.001), citrate (0.740+/-0.217 mmol/kg vs. 0.399+/-0.137 mmol/kg, P < 0.001), pyruvate (0.0659+/-0.0103 mmol/kg vs. 0.0299+/-0.286 mmol/kg, P < 0.001), and numerous amino acid (e.g. alanine, glutamate, isoleucine, leucine, lysine, and valine) concentrations decreased significantly with advancing gestation. A stepwise multiple linear regression model applied to 50 samples showed that gestational age can be accurately predicted using combinations of alanine, glucose and creatinine concentrations.
These results provide key normative data for 2nd and 3rd trimester amniotic fluid metabolite concentrations and provide the foundation for future development of magnetic resonance spectroscopy (MRS) biomarkers to evaluate fetal health and development.
MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 09/2009; 22(6):343-52. · 1.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Electronic REference To access In vivo Concentrations (ERETIC) method was applied to (1)H HR-MAS spectroscopy. The accuracy, precision, and stability of ERETIC as a quantitative reference were evaluated in solution and human prostate tissue samples. For comparison, the reliability of 3-(trimethylsilyl)propionic-2,2,3,3-d(4) acid (TSP) as a quantitation reference was also evaluated. The ERETIC and TSP peak areas were found to be stable in solution over the short-term and long-term, with long-term relative standard deviations (RSDs) of 4.10% and 2.60%, respectively. Quantification of TSP in solution using the ERETIC peak as a reference and a calibrated, rotor-dependent conversion factor yielded results with a precision < or =2.9% and an accuracy error < or =4.2% when compared with the expected values. The ERETIC peak area reproducibility was superior to TSP's reproducibility, corrected for mass, in both prostate surgical and biopsy samples (4.53% vs. 21.2% and 3.34% vs. 31.8%, respectively). Furthermore, the tissue TSP peaks exhibited only 27.5% of the expected area, which would cause an overestimation of metabolite concentrations if used as a reference. The improved quantification accuracy and precision provided by ERETIC may enable the detection of smaller metabolic differences that may exist between individual tissue samples and disease states.
Magnetic Resonance in Medicine 04/2009; 61(3):525-32. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
To evaluate the glycerol to choline ratio as a metabolic indicator of disease severity in nonalcoholic fatty liver disease (NAFLD) with HR-MAS in human liver tissue.
METHOD AND MATERIALS
Committee on Human Research approval was obtained, and the study was in compliance with the Health Insurance Portability and Accountability Act. Twenty liver biopsy samples were obtained from healthy controls (n=5) or nonalcoholic fatty liver disease patients (n=15) demonstrating simple steatosis (n=8), or nonalcoholic steatohepatitis (NASH) (n=7) according to criteria established by the Nonalcoholic Steatohepatitis Clinical Research Network. Tissues were analyzed ex vivo using high resolution magic angle spinning (HR-MAS) MR spectroscopy for correlation with histopathologic variables. One dimensional water-presaturated spectra were acquired at 11.7 T, 10C, and a 2,250 Hz spin rate using a Varian INOVA spectrometer (Palo Alto, CA). Data were analyzed off line using ACD/Labs 1D NMR Processor (ACD/Labs, Toronto) and compared between groups using a Student’s T-test.
The glycerol to choline ratio increased significantly with progression from normal liver (mean = 0.79 + 0.08) to simple steatosis (mean = 2.44 + 1.49, p = 0.017) to NASH (4.11 + 2.45, p = 0.032). The glycerol to noise ratio increased consistently from normal liver to simple steatosis (101%) and from steatosis to NASH (81%), whereas the choline to noise ratio was nearly equal between normal liver and steatosis (2%) but decreased between steatosis and NASH (28%). However, because of the small number of samples neither glycerol nor choline to noise ratios alone were significantly different between normal, steatosis, and NASH.
Our preliminary data suggests increased glycerol and decreased choline observed at high magnetic field strengths may indicate histopathologic disease progression in nonalcoholic fatty liver disease from simple steatosis to steatohepatitis.
Ex vivo HR-MAS liver data suggests increased glycerol and decreased choline may indicate histopathologic disease progression in nonalcoholic fatty liver disease from steatosis to steatohepatitis.
Radiological Society of North America 2008 Scientific Assembly and Annual Meeting; 12/2008
[Show abstract][Hide abstract] ABSTRACT: To determine the intra- and interobserver reproducibility of human amniotic fluid metabolite concentration measurements (including potential markers of fetal lung maturity) detectable by MR spectroscopy.
(1)H high-resolution magic angle spinning (HR-MAS) spectroscopy was performed at 11.7 T on 23 third-trimester amniotic fluid samples. Samples were analyzed quantitatively using 3-(trimethylsilyl)propionic-2,2,3,3-d(4) acid (TSP) as a reference. Four observers independently quantified eight metabolite regions (TSP, lactate doublet and quartet, alanine, citrate, creatinine, choline, and glucose) twice from anonymized, randomized spectra using a semiautomated software program.
Excellent inter- and intraobserver reproducibility was found for all metabolites. Intraclass correlation as a measure of interobserver agreement for the four readers ranged from 0.654 to 0.995. A high correlation of 0.973 was seen for choline in particular, a major component of surfactant. Pearson correlation as a measure of intraobserver reproducibility ranged from 0.478 to 0.999.
Quantification of choline and other metabolite concentrations in amniotic fluid by high-resolution MR spectroscopy can be performed with high inter- and intraobserver reproducibility. Demonstration of reproducible metabolite concentration measurements is a critical first step in the search for biomarkers of fetal lung maturity.
Journal of Magnetic Resonance Imaging 12/2008; 28(6):1540-5. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to investigate the use of lactate and alanine as metabolic biomarkers of prostate cancer using (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy of snap-frozen transrectal ultrasound (TRUS)-guided prostate biopsy tissues. A long-echo-time rotor-synchronized Carr-Purcell-Meiboom-Gill (CPMG) sequence including an electronic reference to access in vivo concentrations (ERETIC) standard was used to determine the concentrations of lactate and alanine in 82 benign and 16 malignant biopsies (mean 26.5% +/- 17.2% of core). Low concentrations of lactate (0.61 +/- 0.28 mmol/kg) and alanine (0.14 +/- 0.06 mmol/kg) were observed in benign prostate biopsies, and there was no significant difference between benign predominantly glandular (N = 54) and stromal (N = 28) biopsies between patients with (N = 38) and without (N = 44) a positive clinical biopsy. In biopsies containing prostate cancer there was a highly significant (P < 0.0001) increase in lactate (1.59 +/- 0.61 mmol/kg) and alanine (0.26 +/- 0.07 mmol/kg), and minimal overlap with lactate concentrations in benign biopsies. This study demonstrates for the first time very low concentrations of lactate and alanine in benign prostate biopsy tissues. The significant increase in the concentration of both lactate and alanine in biopsy tissue containing as little as 5% cancer could be exploited in hyperpolarized (13)C spectroscopic imaging (SI) studies of prostate cancer patients.
Magnetic Resonance in Medicine 10/2008; 60(3):510-6. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A fast and quantitative 2D high-resolution magic angle spinning (HR-MAS) total correlation spectroscopy (TOCSY) experiment was developed to resolve and quantify the choline- and ethanolamine-containing metabolites in human prostate tissues in approximately 1 hr prior to pathologic analysis. At a 40-ms mixing time, magnetization transfer efficiency constants were empirically determined in solution and used to calculate metabolite concentrations in tissue. Phosphocholine (PC) was observed in 11/15 (73%) cancer tissues but only 6/32 (19%) benign tissues. PC was significantly higher (0.39 +/- 0.40 mmol/kg vs. 0.02 +/- 0.07 mmol/kg, z = 3.5), while ethanolamine (Eth) was significantly lower in cancer versus benign prostate tissues (1.0 +/- 0.8 mmol/kg vs. 2.3 +/- 1.9 mmol/kg, z = 3.3). Glycerophosphocholine (GPC) (0.57 +/- 0.87 mmol/kg vs. 0.29 +/- 0.26 mmol/kg, z = 1.2), phosphoethanolamine (PE) (4.4 +/- 2.2 mmol/kg vs. 3.4 +/- 2.6 mmol/kg, z = 1.4), and glycerophosphoethanolamine (GPE) (0.54 +/- 0.82 mmol/kg vs. 0.15 +/- 0.15 mmol/kg, z = 1.8) were higher in cancer versus benign prostate tissues. The ratios of PC/GPC (3.5 +/- 4.5 vs. 0.32 +/- 1.4, z = 2.6), PC/PE (0.08 +/- 0.08 vs. 0.01 +/- 0.03, z = 3.5), PE/Eth (16 +/- 22 vs. 2.2 +/- 2.0, z = 2.4), and GPE/Eth (0.41 +/- 0.51 vs. 0.06 +/- 0.06, z = 2.6) were also significantly higher in cancer versus benign tissues. All samples were pathologically interpretable following HR-MAS analysis; however, degradation experiments showed that PC, GPC, PE, and GPE decreased 7.7 +/- 2.2%, while Cho+mI and Eth increased 18% in 1 hr at 1 degrees C and a 2250 Hz spin rate.
Magnetic Resonance in Medicine 08/2008; 60(1):33-40. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To retrospectively compare relative accuracy of different interpretative approaches to magnetic resonance (MR) and MR spectroscopic imaging of peripheral zone prostate cancer, by using histologic examination results as the reference standard.
This HIPAA-compliant study had institutional Committee on Human Research approval, with waiver of written consent requirement. Spectroscopic voxels of unequivocally benign (n = 66) or malignant (n = 77) peripheral zone tissue were identified by using step-section histopathologic tumor maps created for 28 men (mean age, 60 years; range, 46-71 years) who underwent endorectal MR and MR spectroscopic imaging before radical prostatectomy. Two readers (9 and 8 years of experience) independently scored the selected voxels on a scale from 1 (likely benign) to 5 (likely malignant) at randomized review of the corresponding tissue outlined on a transverse T2-weighted MR image (T2 approach), the MR spectrum from the selected voxel only (single-voxel approach), the MR spectra from all voxels at the same axial level (multivoxel approach), and both the corresponding tissue outlined on a transverse T2-weighted image and the MR spectra from all voxels at the same axial level (integrated approach). Readers were aware that spectra were derived in patients with biopsy-proved diagnoses of prostate cancer and represented either benign or malignant tissue but were unaware of which voxels had been labeled benign or malignant and of all other clinical, histopathologic, and MR imaging findings. Receiver operating characteristic (ROC) curve analysis was performed. Generalized estimating equation method was used to estimate sensitivity and specificity for specific cutoff values.
Mean areas under the ROC curve (AUCs) for the T2, single-voxel, multivoxel, and integrated approaches were 0.69, 0.72, 0.72, and 0.76, respectively. AUC of the integrated approach was significantly higher than those of the other three approaches (P < .001). kappa Values for assessment of interobserver variability for the T2, single-voxel, multivoxel, and integrated approaches were 0.39, 0.39, 0.34, and 0.48, respectively.
Addition of MR spectroscopic imaging to MR imaging significantly improves characterization of peripheral zone prostate tissue as benign or malignant; improved performance is obtained when both data sets are interpreted in an integrated fashion.
[Show abstract][Hide abstract] ABSTRACT: LEARNING OBJECTIVES
Understand the potential and limitations of using 1.5T magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) and the improvements provided by a multi-parametric (anatomic, spectroscopic, diffusion and perfusion) imaging approach at 3T for detecting and characterizing prostate cancer prior to and after therapy.
Published 1.5T magnetic resonance imaging and magnetic resonance spectroscopic imaging studies of prostate cancer patients have indicated significant clinical value in detecting and characterizing prostate cancer prior to and after therapy. Commercial combined 1.5T MRI/MRSI exams are currently available and a growing number of published studies have indicated it's utility in the selection of the most appropriate therapy for individual patients and for providing early imaging biomarkers of therapeutic success and failure. However, recent studies have also demonstrated limitations in detecting small volume (< 0.5 cc) low grade (≤ 3+3) prostate cancer and distinguishing prostate cancer from other benign prostatic pathologies such as prostatitis and benign prostatic hyperplasia. However, the use of higher field MR scanners (3T), addition of other functional information (diffusion and dynamic contrast weighted imaging), new spectroscopic biomarkers, and more sensitive spectroscopic imaging techniques (hyperoplarized 13C MRSI) have demonstrated the potential to overcome current limitations. In this lecture, the potential and limitations of 1.5T MRI/MRSI for therapeutic selection and monitoring and the improvements obtainable using a multi-parametric imaging approach at 3T will be presented.
Radiological Society of North America 2007 Scientific Assembly and Annual Meeting; 11/2007
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to determine respective associations between prostatic citrate or metabolic atrophy (no detectable citrate, choline, and creatine) at magnetic resonance spectroscopy (MRS) and time on hormone-deprivation therapy, serum PSA, and biopsy Gleason score. Clinical data, histopathology reports and PSA levels of 36 patients on hormone-deprivation therapy (age, 64+/-9 years, pre-therapeutic biopsy Gleason sum, median 6, range 3-8, antiandrogens only, n=3, LHRH-analogues only, n=4, combined hormone-deprivation therapy, n=29, duration, 27+/-19 weeks) for locally confined prostate cancer (PCA) were retrospectively correlated with findings in the peripheral zone of the prostate at 3D-MRS (endorectal coil, PRESS, TR 1,000 ms, TE 130 ms). The results show that citrate was usually detected after 13 weeks or less of hormone-deprivation therapy (10/12 vs. 6/24 patients, chi-square-test, p=0.002). All patients with PSA levels exceeding 0.20 ng/ml had detectable metabolites (citrate, n=12, choline without citrate, n=6), while 9/18 patients with PSA 0.20 ng/ml or less showed metabolic atrophy (Fisher-exact-test, p=0.001). There were no significant associations between citrate, metabolic atrophy, pre-therapeutic PSA, and biopsy Gleason sum, respectively. It has been concluded that hormone-deprivation therapy for locally confined PCA has not reached its full deprivation potential after 13 weeks. MRS detects prostate metabolism in patients with PSA exceeding 0.20 ng/ml after hormone-deprivation therapy.
European Radiology 03/2007; 17(2):371-8. · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A method was developed to quantify prostate metabolite concentrations using (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy. T(1) and T(2) relaxation times (in milliseconds) were determined for the major prostate metabolites and an internal TSP standard, and used to optimize the acquisition and repetition times (TRs) at 11.7 T. At 1 degrees C, polyamines (PAs; T(1mean) = 100 +/- 13, T(2mean) = 30.8 +/- 7.4) and citrate (Cit; T(1mean) = 237 +/- 39, T(2mean) = 68.1 +/- 8.2) demonstrated the shortest relaxation times, while taurine (Tau; T(1mean) = 636 +/- 78, T(2mean) = 331 +/- 71) and choline (Cho; T(1mean) = 608 +/- 60, T(2mean) = 393 +/- 81) demonstrated the longest relaxation times. Millimolal metabolite concentrations were calculated for 60 postsurgical tissues using metabolite and TSP peak areas, and the mass of tissue and TSP. Phosphocholine plus glycerophosphocholine (PC+GPC), total choline (tCho), lactate (Lac), and alanine (Ala) concentrations were higher in prostate cancer ([PC+GPC](mean) = 9.34 +/- 6.43, [tCho](mean) = 13.8 +/- 7.4, [Lac](mean) = 69.8 +/- 27.1, [Ala](mean) = 12.6 +/- 6.8) than in healthy glandular ([PC+GPC](mean) = 3.55 +/- 1.53, P < 0.01; [tCho](mean) = 7.06 +/- 2.36, P < 0.01; [Lac](mean) = 46.5 +/- 17.4, P < 0.01; [Ala](mean) = 8.63 +/- 4.91, P = 0.051) and healthy stromal tissues ([PC+GPC](mean) = 4.34 +/- 2.46, P < 0.01; [tCho](mean) = 7.04 +/- 3.10, P < 0.01; [Lac](mean) = 45.1 +/- 18.6, P < 0.01; [Ala](mean) = 6.80 +/- 2.95, P < 0.01), while Cit and PA concentrations were significantly higher in healthy glandular tissues ([Cit](mean) = 43.1 +/- 21.2, [PAs](mean) = 18.5 +/- 15.6) than in healthy stromal ([Cit](mean) = 16.1 +/- 5.6, P < 0.01; [PAs](mean) = 3.15 +/- 1.81, P < 0.01) and prostate cancer tissues ([Cit](mean) = 19.6 +/- 12.7, P < 0.01; [PAs](mean) = 5.28 +/- 5.44, P < 0.01). Serial spectra acquired over 12 hr indicated that the degradation of Cho-containing metabolites was minimized by acquiring HR-MAS data at 1 degree C compared to 20 degrees C.
Magnetic Resonance in Medicine 07/2006; 55(6):1257-64. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amniocentesis is an invasive procedure with inherent risks. Magnetic resonance (MR) spectroscopy is a safe noninvasive way of measuring levels of choline-containing compounds (including surfactant) and other metabolites. The purpose of this study was to test the feasibility of assessing fetal lung maturity in vivo and ex vivo using MR spectroscopy to determine differences in amniotic fluid choline concentrations between the second and third trimesters.
Magnetic resonance spectroscopy was performed on ex vivo samples of amniotic fluid from second- and third-trimester fetuses. In vivo MR spectroscopy was performed on amniotic fluid and fetal lungs in third-trimester fetuses. Spectral acquisition and analysis were performed by an attending radiologist in conjunction with an MR spectroscopist.
Choline-containing compounds were observed from 3.20 to 3.25 ppm. Comparison of spectra from second- and third-trimester amniocentesis revealed a trend toward increased choline at later gestational ages. Spectra from amniotic fluid and lungs of a third-trimester fetus showed that choline can be detected in the in vivo setting.
Magnetic resonance spectroscopy is a safe noninvasive procedure that enables measurement of choline-containing compounds in fetal lung and amniotic fluid. Magnetic resonance spectroscopy shows a trend toward an increased quantity of choline in third- vs second-trimester amniocentesis.
Journal of Pediatric Surgery 05/2006; 41(4):768-73. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper compares two spectral processing methods for obtaining quantitative measures from in vivo prostate spectra, evaluates their effectiveness, and discusses the necessary modifications for accurate results. A frequency domain analysis (FDA) method based on peak integration was compared with a time domain fitting (TDF) method, a model-based nonlinear least squares fitting algorithm. The accuracy of both methods at estimating the choline + creatine + polyamines to citrate ratio (CCP:C) was tested using Monte Carlo simulations, empirical phantom MRSI data and in vivo MRSI data. The paper discusses the different approaches employed to achieve the quantification of the overlapping choline, creatine and polyamine resonances. Monte Carlo simulations showed induced biases on the estimated CCP:C ratios. Both methods were successful in identifying tumor tissue, provided that the CCP:C ratio was greater than a given (normal) threshold. Both methods predicted the same voxel condition in 94% of the in vivo voxels (68 out of 72). Both TDF and FDA methods had the ability to identify malignant voxels in an artifact-free case study using the estimated CCP:C ratio. Comparing the ratios estimated by the TDF and the FDA, the methods predicted the same spectrum type in 17 out of 18 voxels of the in vivo case study (94.4%).
NMR in Biomedicine 05/2006; 19(2):188-97. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this chapter, we describe the current and potential role of magnetic resonance spectroscopy (MRS) and magnetic resonance
spectroscopic imaging (MRSI) in organs of the body with an emphasis on the technical aspects of applications in prostate and
breast cancer, and diseases of the liver. In contrast to anatomical magnetic resonance imaging (MRI), which detects changes
in the relaxivity or density of bulk tissue water, spectroscopy detects small molecular weight metabolites within the cytosol
of cells or within extracellular spaces such as glands or ducts. The addition of spectroscopy has been shown to improve the
ability (i.e. sensitivity, specificity, and accuracy ) of conventional MRI to detect and stage prostate and breast cancer
[2-4] and has shown promise in the evaluation of primary and metastatic liver tumors  and other liver diseases [6,7]. However,
the potential of spectroscopy is even greater because multiple metabolic markers may be combined to provide an independent
assessment of disease state, cancer aggressiveness, and therapeutic response [8-10]. The clinical use of spectroscopy as an
adjunct to MRI has expanded dramatically over the past several years. This has been due to both the need to answer clinically
relevant questions and recent technical advances in hardware and software that have provided improvements in the spatial and
time resolution of the spectral data and have resulted in the incorporation of this technology on commercial MR scanners.
These breakthroughs have allowed the routine addition of spectroscopy sequences to clinical MRI exams, and have led to spectroscopy
being factored into the clinical decision process.
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to determine the ability of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to distinguish different stages of intervertebral disc degeneration (IVDD). 17 discs were removed from human cadavers and analyzed them using 1D and 2D (total correlation spectroscopy (TOCSY)) (1)H HR-MAS spectroscopy, and T(1) and T(2) relaxation time measurements to determine the chemical composition and changes in chemical environment of discs with increasing levels of degeneration (Thompson grade). Among the significant findings were that spectra were very similar for samples taken from annular and nuclear regions of discs, and that visually apparent changes were observed in the spectra of the annular and nuclear samples from discs with increasing Thompson grade. Area ratios of the N-acetyl to choline (Cho) regions, and Cho to carbohydrate (Carb) regions of the spectra allowed us to discriminate between discs of increasing Thompson grade with minimal overlap of individual ratios. Changes in T(1) and T(2) relaxation times of the chemical constituents of disc spectra were not significantly correlated to the degree of degeneration. The results of this study support the feasibility of using in vivo spectroscopy for detecting chemical changes associated with disc degeneration.
Magnetic Resonance in Medicine 04/2005; 53(3):519-27. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A rotor-synchronized WURST-8 adiabatic pulse scheme was compared to the conventional MLEV-17 hard pulse scheme for isotropic mixing in total correlation spectroscopy (TOCSY) studies of intact human prostate tissues under high-resolution magic angle spinning (HR-MAS) conditions. Both mixing schemes were extremely sensitive to the rotational resonance condition and dramatic reductions in signal to noise were observed when pulse durations deviated from 1/(spin rate). A significant increase in cross-peak intensities was observed using rotor-synchronized WURST-8 adiabatic pulses versus those observed using the rotor-synchronized MLEV-17 hard pulse scheme in both solution and tissue. In tissue, absolute signal intensities ranged from 1.5x to 10.5x greater (average: 4.75x) when WURST-8 was used in place of MLEV-17. Moreover, the difference was so dramatic that several metabolite cross peaks observed using WURST-8 pulses were not observed using MLEV-17 pulses, including cross peaks corresponding to many of the choline- and ethanolamine-containing metabolites. Due to the complex modulation of TOCSY cross peaks for multiply coupled spins and the shorter T(2) relaxation times of tissue metabolites, maximum cross-peak intensities occurred at shorter mixing times than predicted by theory. In summary, a WURST-8 adiabatic mixing scheme produced significantly greater absolute cross-peak signal intensities than MLEV-17 hard pulse mixing, and maximum cross-peak intensity versus mixing time must be established for specific spin systems and T(2) relaxation times.
Magnetic Resonance in Medicine 02/2005; 53(1):41-8. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the accuracy and interobserver variability of a standardized evaluation system for endorectal three-dimensional (3D) magnetic resonance (MR) spectroscopic imaging of the prostate.
The human research committee approved the study, and all patients provided written informed consent. Endorectal MR imaging and MR spectroscopic imaging were performed in 37 patients before they underwent radical prostatectomy. For the 22 patients with good or excellent MR spectroscopic imaging data, step-section histopathologic tumor maps were used to identify spectroscopic voxels of unequivocally benign (n = 306) or malignant (n = 81) peripheral zone tissue. Two independent spectroscopists, unaware of all other findings, scored the spectra of the selected voxels by using a scale of 1 (benign) to 5 (malignant) that was based on standardized metabolic criteria. Descriptive statistical, receiver operating characteristics (ROC), and kappa statistical analyses of the data obtained by both readers were performed by using two definitions of cancer: one based on a voxel score of 3-5 and the other based on a score of 4 or 5.
The scoring system had good accuracy (74.2%-85.0%) in the differentiation between benign and malignant tissue voxels, with areas under the ROC curve of 0.89 for reader 1 and 0.87 for reader 2. Specificities of 84.6% and 89.3% were achieved when a voxel score of 4 or 5 was used to identify cancer, and sensitivities of 90% and 93% were achieved when a score of 3-5 was used to identify cancer. Readers demonstrated excellent interobserver agreement (kappa values, 0.79 and 0.80).
The good accuracy and excellent interobserver agreement achieved by using the standardized five-point scale to interpret peripheral zone metabolism demonstrate the potential effectiveness of using metabolic information to identify prostate cancer, and the clinical usefulness of this system warrants testing in prospective clinical trials of MR imaging combined with MR spectroscopic imaging.
[Show abstract][Hide abstract] ABSTRACT: To evaluate endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging for the depiction of locally recurrent prostate cancer after external beam radiation therapy.
Endorectal MR imaging and MR spectroscopic imaging were performed in 21 patients with biochemical failure after external beam radiation therapy for prostate cancer. Two readers independently and retrospectively reviewed MR images and rated the likelihood of recurrent tumor on a five-point scale. Spectroscopic voxels were considered suspicious for malignancy if the choline level was elevated and citrate was absent. Receiver operating characteristic curve analysis was used to assess cancer detection in each side of the prostate with endorectal MR imaging and spectroscopic imaging at different thresholds based on the scores assigned by the two readers and on the number of suspicious voxels in each hemiprostate, respectively. The presence or absence of cancer at subsequent transrectal biopsy was used as the standard of reference.
Biopsy demonstrated locally recurrent prostate cancer in nine hemiprostates in six patients. The area under the receiver operating characteristic curve for the detection of locally recurrent cancer with MR imaging was 0.49 and 0.51 for readers 1 and 2, respectively. By using the number of suspicious voxels to define different diagnostic thresholds, the area under the receiver operating characteristic curve for MR spectroscopic imaging was significantly (P < .005) higher, at 0.81. In particular, the presence of three or more suspicious voxels in a hemiprostate showed a sensitivity and specificity of 89% and 82%, respectively, for the diagnosis of local recurrence. Seven hemiprostates demonstrated complete metabolic atrophy at spectroscopic imaging and only postirradiation atrophy at biopsy.
Preliminary data suggest that MR spectroscopic imaging, but not endorectal MR imaging, may be of value for the depiction of locally recurrent prostate cancer after radiation therapy.