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Northeastern North America has been experiencing warmer winters with reduced snow accumulation, with more frequent winter freeze–thaw cycles. We conducted a laboratory experiment to investigate how increased frequency of freeze–thaw cycles (FTC) would alter soil C and N availability. Organic (O) and mineral (B) horizon soils were collected from a coniferous forest in Maine, processed to exclude roots, and then frozen in the laboratory (−10 °C) with one (FTC-1), two (FTC-2), or six (FTC-6) thaw periods (+5 °C). Soils were analyzed for extractable ammonium (NH4-N), water extractable organic carbon (WEOC), carbon dioxide flux (respiration), and total C and N. Extractable NH4-N increased following FTC (all levels), for both horizons. While WEOC concentrations did not change for FTC vs. control, the WEOC in O horizons had a lower SUVA254 in FTC soils compared to control, indicating a stronger microbial influence (i.e., microbial cell lysis) in these soils after FTC. Respiration in O horizon soils decreased post-incubation and did not differ between FTC and Control soils. In the B horizon, however, FTC soils showed greater respiration than Control soils, suggesting that the newly available nutrients may have stimulated microbial activity. In contrast to these results, total C and N remained unaltered by FTC, presumably because the FTC disturbances represented mostly a translocation of C and N from one pool into another, and losses due to respiration were too small to significantly influence the large TC and TN pools. The effect of FTC on NH4-N did not change with FTC frequency, suggesting that a single FTC is sufficient to alter both C and N availability and/or quality, and that additional FTC may not have a significant further effect. This study provides fresh insights on how organic and mineral horizon soils might respond to increased freeze–thaw frequency in winter.

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of 13 C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1- 13 C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1- 13 C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in 13 C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.

In vivo MRSI is an important imaging modality that has been shown in numerous research studies to give biologically relevant information for assessing the underlying mechanisms of disease and for monitoring response to therapy. The increasing availability of high field scanners and multichannel radiofrequency coils has provided the opportunity to acquire in vivo data with significant improvements in sensitivity and signal to noise ratio. These capabilities may be used to shorten acquisition time and provide increased coverage. The ability to acquire rapid, volumetric MRSI data is critical for examining heterogeneity in metabolic profiles and for relating serial changes in metabolism within the same individual during the course of the disease. In this review we discuss the implementation of strategies that use alternative k-space sampling trajectories and parallel imaging methods in order to speed up data acquisition. The impact of such methods is demonstrated using three recent examples of how these methods have been applied. These are to the acquisition of robust 3D (1)H MRSI data within 5-10 min at a field strength of 3 T, to obtaining higher sensitivity for (1)H MRSI at 7 T and to using ultrafast volumetric and dynamic (13)C MRSI for monitoring the changes in signals that occur following the injection of hyperpolarized (13)C agents.

Objective: The objective of this study was to determine whether metabolic parameters derived from ex vivo analysis of tissue samples are predictive of biologic characteristics of recurrent low grade gliomas (LGGs). This was achieved by exploring the use of multivariate pattern recognition methods to generate statistical models of the metabolic characteristics of recurrent LGGs that correlate with aggressive biology and poor clinical outcome. Methods: Statistical models were constructed to distinguish between patients with recurrent gliomas that had undergone malignant transformation to a higher grade and those that remained grade 2. The pattern recognition methods explored in this paper include three filter-based feature selection methods (chi-square, gain ratio, and two-way conditional probability), a genetic search wrapper-based feature subset selection algorithm, and five classification algorithms (linear discriminant analysis, logistic regression, functional trees, support vector machines, and decision stump logit boost). The accuracy of each pattern recognition framework was evaluated using leave-one-out cross-validation and bootstrapping. Materials: The population studied included fifty-three patients with recurrent grade 2 gliomas. Among these patients, seven had tumors that transformed to grade 4, twenty-four had tumors that transformed to grade 3, and twenty-two had tumors that remained grade 2. Image-guided tissue samples were obtained from these patients using surgical navigation software. Part of each tissue sample was examined by a pathologist for histological features and for consistency with the tumor grade diagnosis. The other part of the tissue sample was analyzed with ex vivo nuclear magnetic resonance (NMR) spectroscopy. Results: Distinguishing between recurrent low grade gliomas that transformed to a higher grade and those that remained grade 2 was achieved with 96% accuracy, using areas of the ex vivo NMR spectrum corresponding to myoinositol, 2-hydroxyglutarate, hypo-taurine, choline, glycerophosphocholine, phosphocholine, glutathione, and lipid. Logistic regression and decision stump boosting models were able to distinguish between recurrent gliomas that transformed to a higher grade and those that did not with 100% training accuracy (95% confidence interval [93-100%]), 96% leave-one-out cross-validation accuracy (95% confidence interval [87-100%]), and 96% bootstrapping accuracy (95% confidence interval [95-97%]). Linear discriminant analysis, functional trees, and support vector machines were able to achieve leave-one-out cross-validation accuracy above 90% and bootstrapping accuracy above 85%. The three feature ranking methods were comparable in performance. Conclusions: This study demonstrates the feasibility of using quantitative pattern recognition methods for the analysis of metabolic data from brain tissue obtained during the surgical resection of gliomas. All pattern recognition techniques provided good diagnostic accuracies, though logistic regression and decision stump boosting slightly outperform the other classifiers. These methods identified biomarkers that can be used to detect malignant transformations in individual low grade gliomas, and can lead to a timely change in treatment for each patient.

Purpose To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

A practical multinuclear transceiver RF volume coil with improved efficiency for in vivo small animal (1)H/(13)C/(23)Na MR applications at the ultrahigh magnetic field of 7 T is reported. In the proposed design, the coil's resonance frequencies for (1)H and (13)C are realized by using a traditional double-tuned approach, while the resonant frequency for (23)Na, which is only some 4 MHz away from the (13)C frequency, is tuned based upon (13)C channel by easy-operating capacitive "frequency switches". In contrast to the traditional triple-tuned volume coil, the volume coil with the proposed design possesses less number of resonances, which helps improve the coil efficiency and alleviate the design and operation difficulties. This coil design strategy is advantageous and well suitable for multinuclear MR imaging and spectroscopy studies, particularly in the case where Larmor frequencies of nuclei in question are not separate enough. The prototype multinuclear coil was demonstrated in the desired unshielded design for easy construction and experiment implementation at 7 T. The design method may provide a practical and robust solution to designing multinuclear RF volume coils for in vivo MR imaging and spectroscopy at ultrahigh fields. Finite difference time domain method simulations for evaluating the design and 7-T MR experiment results acquired using the prototype coil are presented.

We report metabolic images of 13C, following injection of a bolus of hyperpolarized [1-13C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.

Detection of glutathione (GSH) is technically challenging at clinical field strengths of 1.5 or 3 T due to its low concentration in the human brain coupled with the fact that conventional single-echo acquisitions, typically used for magnetic resonance (MR) spectroscopy acquisitions, cannot be used to resolve GSH given its overlap with other resonances. In this study, an MR spectral editing scheme was used to generate an unobstructed detection of GSH at 7 T. This technique was used to obtain normative white (WM) and gray matter (GM) GSH concentrations over a two-dimensional region. Results indicated that GSH was significantly higher (P

BACKGROUND AND PURPOSE: The purpose of this study was to derive quantitative parameters from magnetic resonance (MR) spectroscopic, perfusion, and diffusion imaging of grade 2 gliomas according to the World Health Organization and to investigate how these multiple imaging modalities can contribute to evaluating their histologic subtypes and spatial characteristics. MATERIALS AND METHODS: MR spectroscopic, perfusion, and diffusion images from 56 patients with newly diagnosed grade 2 glioma (24 oligodendrogliomas, 18 astrocytomas, and 14 oligoastrocytomas) were retrospectively studied. Metabolite intensities, relative cerebral blood volume (rCBV), and apparent diffusion coefficient (ADC) were statistically evaluated. RESULTS: The 75th percentile rCBV and median ADC were significantly different between oligodendrogliomas and astrocytomas (P < .0001) and between oligodendrogliomas and oligoastrocytomas (P < .001). Logistic regression analysis identified both 75th percentile rCBV and median ADC as significant variables in the differentiation of oligodendrogliomas from astrocytomas and oligoastrocytomas. Group differences in metabolite intensities were not significant, but there was a much larger variation in the volumes and maximum values of metabolic abnormalities for patients with oligodendroglioma compared with the other tumor subtypes. CONCLUSIONS: Perfusion and diffusion imaging provide quantitative MR parameters that can help to differentiate grade 2 oligodendrogliomas from grade 2 astrocytomas and oligoastrocytomas. The large variations in the magnitude and spatial extent of the metabolic lesions between patients and the fact that their values are not correlated with the other imaging parameters indicate that MR spectroscopic imaging may provide complementary information that is helpful in targeting therapy, evaluating residual disease, and assessing response to therapy.

Susceptibility-weighted imaging (SWI) is a valuable technique for high-resolution imaging of brain vasculature that greatly benefits from the emergence of higher field strength MR scanners. Autocalibrating partially parallel imaging techniques can be employed to reduce lengthy acquisition times as long as the decrease in signal-to-noise ratio does not significantly affect the contrast between vessels and brain parenchyma. This study assessed the feasibility of a Generalized Autocalibrating Partially Parallel Acquisition (GRAPPA)-based SWI technique at 7 T in both healthy volunteers and brain tumor patients. GRAPPA-based SWI allowed a twofold or more reduction in scan time without compromising vessel contrast and small vessel detection. Postprocessing parameters for the SWI needed to be modified for patients where the tumor causes high-frequency phase wrap artifacts but did not adversely affect vessel contrast. GRAPPA-based SWI at 7 T revealed regions of microvascularity, hemorrhage and calcification within heterogeneous brain tumors that may aid in characterizing active or necrotic tumor and monitoring treatment effects.

The development of dynamic nuclear polarization (DNP) in solution has enabled in vivo 13C MR studies at high signal to noise ratio (SNR) following injection of pre-polarized 13C substrates. While prior studies have demonstrated the ability to observe metabolism following injection of hyperpolarized 13C-pyruvate, the goal of this study was to develop and test a new hyperpolarized agent for investigating in vivo metabolism, [1-13C] lactate. A preparation for pre-polarized 13C-lactate and the requisite dissolution media were developed to investigate the feasibility for in vivo 13C MRS/MRSI studies following injection of this hyperpolarized agent. This study demonstrated, for the first time, not only the ability to detect hyperpolarized [1-13C] lactate in vivo, but also the metabolic products 13C pyruvate, 13C alanine and 13C bicarbonate following injection in normal rats. Using 13C-lactate as a substrate provided the ability to study the conversion of lactate to pyruvate in vivo and to detect the secondary conversions to alanine and bicarbonate through pyruvate. This study also demonstrated the potential value of this hyperpolarized agent to investigate in vivo lactate uptake and metabolism in pre-clinical animal models.

Dynamic nuclear polarization and dissolution of a 13C-labeled substrate enables the dynamic imaging of cellular metabolism. Spectroscopic information is typically acquired, making the acquisition of dynamic volumetric data a challenge. To enable rapid volumetric imaging, a spectral-spatial excitation pulse was designed to excite a single line of the carbon spectrum. With only a single resonance present in the signal, an echo-planar readout trajectory could be used to resolve spatial information, giving full volume coverage of 32 × 32 × 16 voxels every 3.5 seconds. This high frame rate was used to measure the different lactate dynamics in different tissues in a normal rat model and a mouse model of prostate cancer.

High polarization of nuclear spins in liquid state through dynamic nuclear polarization has enabled the direct monitoring of 13C metabolites in vivo at very high signal to noise, allowing for rapid assessment of tissue metabolism. The abundant SNR afforded by this hyperpolarization technique makes high resolution 13C 3D-MRSI feasible. However, the number of phase encodes that can be fit into the short acquisition time for hyperpolarized imaging limits spatial coverage and resolution. To take advantage of the high SNR available from hyperpolarization, we have applied compressed sensing to achieve a factor of 2 enhancement in spatial resolution without increasing acquisition time or decreasing coverage. In this paper, the design and testing of compressed sensing suited for a flyback 13C 3D-MRSI sequence are presented. The key to this design was the undersampling of spectral k-space using a novel blipped scheme, thus taking advantage of the considerable sparsity in typical hyperpolarized 13C spectra. Phantom tests validated the accuracy of the compressed sensing approach and initial mouse experiments demonstrated in vivo feasibility.

Objective: The purpose of this study was to develop a pattern classification algorithm for use in predicting the location of new contrast-enhancement in brain tumor patients using data obtained via multivariate magnetic resonance (MR) imaging from a prior scan. We also explore the use of feature selection or weighting in improving the accuracy of the pattern classifier. Methods and materials: Contrast-enhanced MR images, perfusion images, diffusion images, and proton spectroscopic imaging data were obtained from 26 patients with glioblastoma multiforme brain tumors, divided into a design set and an unseen test set for verification of results. A k-NN algorithm was implemented to classify unknown data based on a set of training data with ground truth derived from post-treatment contrast-enhanced images; the quality of the k-NN results was evaluated using a leave-one-out cross-validation method. A genetic algorithm was implemented to select optimal features and feature weights for the k-NN algorithm. The binary representation of the weights was varied from 1 to 4bits. Each individual parameter was thresholded as a simple classification technique, and the results compared with the k-NN. Results: The feature selection k-NN was able to achieve a sensitivity of 0.78+/-0.18 and specificity of 0.79+/-0.06 on the holdout test data using only 7 of the 38 original features. Similar results were obtained with non-binary weights, but using a larger number of features. Overfitting was also observed in the higher bit representations. The best single-variable classifier, based on a choline-to-NAA abnormality index computed from spectroscopic data, achieved a sensitivity of 0.79+/-0.20 and specificity of 0.71+/-0.11. The k-NN results had lower variation across patients than the single-variable classifiers. Conclusions: We have demonstrated that the optimized k-NN rule could be used for quantitative analysis of multivariate images, and be applied to a specific clinical research question. Selecting features was found to be useful in improving the accuracy of feature weighting algorithms and improving the comprehensibility of the results. We believe that in addition to lending insight into parameter relevance, such algorithms may be useful in aiding radiological interpretation of complex multimodality datasets.

Atmospheric mercury (Hg) is delivered to ecosystems via rain, snow, cloud/fog, and dry deposition. The importance of snow, especially snow that has passed through the forest canopy (throughfall), in delivering Hg to terrestrial ecosystems has received little attention in the literature. The snowpack is a dynamic system that links atmospheric deposition and ecosystem cycling through deposition and emission of deposited Hg. To examine the magnitude of Hg delivery via snowfall, and to illuminate processes affecting Hg flux to catchments during winter (cold season), Hg in snow in no-canopy areas and under forest canopies measured with four collection methods were compared: (1) Hg in wet precipitation as measured by the Mercury Deposition Network (MDN) for the site in Acadia National Park, Maine, USA, (2) event throughfall (collected after snowfall cessation for accumulations of >8 cm), (3) season-long throughfall collected using the same apparatus for event sampling but deployed for the entire cold season, and (4) snowpack sampling. Estimates (mean ± SE) of Hg deposition using these methods during the 91-day cold season in 2004–2005 at conifer sites showed that season-long throughfall Hg flux (1.80 μg/m2)

The increased susceptibility effects and high signal-to-noise ratio at 7.0 T enable imaging of the brain using the phase of the magnetic resonance signal. This study describes and evaluates a robust method for calculating phase images from gradient-recalled echo (GRE) scans. The GRE scans were acquired at 7.0 T using an eight-channel receive coil at spatial resolutions up to 0.195 x 0.260 x 2.00 mm. The entire 7.0 T protocol took less than 10 min. Data were acquired from forty-seven subjects including clinical patients with multiple sclerosis (MS) or brain tumors. The phase images were post-processed using a fully automated phase unwrapping algorithm that combined the data from the different channels. The technique was used to create the first phase images of MS patients at any field strength and the first phase images of brain tumor patients above 1.5 T. The clinical images showed novel contrast in MS plaques and depicted microhemorrhages and abnormal vasculature in brain tumors with unsurpassed resolution and contrast.

Purpose: To determine whether the combined magnetic resonance imaging (MRI) and magnetic resonance spectroscopy imaging (MRSI) before radiation therapy (RT) is valuable for RT target definition, and to evaluate the feasibility of replacing the current definition of uniform margins by custom-shaped margins based on the information from MRI and MRSI. Methods and Materials: A total of 23 glioblastoma multiforme (GBM) patients underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT and at 2-month follow-up intervals thereafter. The MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a measure of spectroscopic abnormality. A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity, and CNI2 (CNI ≥ 2) based on the pre-RT imaging was compared to the extent of CNI2 and the RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared with the extent of CE at each follow-up. Results: Nine patients showed new or increased CE during follow-up, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6 patients and within the CNI2 that was not entirely covered by 60 Gy in 3 patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9) of the patients with new or increased CE. Conclusion: These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting.

Dynamic nuclear polarization of metabolically active compounds labeled with 13 C has been introduced as a means for imaging metabolic processes in vivo . To differentiate between the injected compound and the various metabolic products, an imaging technique capable of separating the different chemical-shift species must be used. In this paper, the design and testing of a pulse sequence for rapid magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13 C is presented. The pulse sequence consists of a small-tip excitation followed by a double spin echo using adiabatic refocusing pulses and a “flyback” echo-planar readout gradient. Key elements of the sequence are insensitivity to calibration of the transmit gain, the formation of a spin echo giving high-quality spectral information, and a small effective tip angle that preserves the magnetization for a sufficient duration. Experiments in vivo showed three-dimensional coverage with excellent spectral quality and SNR.

This paper presents the initial steps taken to integrate the University of California at San Francisco Radiology Department's magnetic resonance (MR) scanners with its high-performance computing (HPC) grid. The objective is to improve patient care by enabling near real-time, computationally intensive medical image processing, directly at an MR scanner. A graphical software tool is described that was developed to run on the MR scanners for submitting processing jobs to the Departmental grid. The computationally intensive parallel reconstruction and quantification of large, multi-dimensional MR spectroscopic imaging (MRSI) data sets was used as the prototype application for this system. Initial results indicate that real-time processing of medical imaging data on a shared HPC resource is reliable and possible in a clinically acceptable time of less than 5min. The Department's HPC resource is comprised of hardware owned by multiple research groups at three separate University facilities throughout San Francisco.

The purpose of this study was to assess the benefits of a 3 T scanner and an eight-channel phased-array head coil for acquiring three-dimensional PRESS (Point REsolved Spectral Selection) proton (H-1) magnetic resonance spectroscopic imaging (MRSI) data from the brains of volunteers and patients with brain tumors relative to previous studies that used a 1.5 T scanner and a quadrature head coil. Issues that were of concern included differences in chemical shift artifacts, line broadening due to increased susceptibility at higher field strengths, changes in relaxation times and the increased complexity of the postprocessing software due to the need for combining signals from the multichannel data. Simulated and phantom spectra showed that very selective suppression pulses with a thickness of 40 mm and an overpress factor of at least 1.2 are needed to reduce chemical shift artifact and lipid contamination at higher field strengths. Spectral data from a phantom and those from six volunteers demonstrated that the signal-to-noise ratio (SNR) in the eight-channel coil was more than 50% higher than that in the quadrature head coil. For healthy volunteers and eight patients with brain tumors, the SNR at 3 T with the eight-channel coil was on average 1.5 times higher relative to the eight-channel coil at 1.5 T in voxels from normal-appearing brains. In combination with the effect of a higher field strength, the use of the eight-channel coil was able to provide an increase in the SNR of more than 2.33 times the corresponding acquisition at 1.5 T with a quadrature head coil. This is expected to be critical for clinical applications of MRSI in patients with brain tumors because it can be used to either decrease acquisition time or improve spatial resolution.

Glutamate and glutamine are important neurochemicals in the central nervous system and the neurotoxic properties of excess glutamate have been associated with several neurodegenerative diseases. The TE-Averaged PRESS technique has been shown by our group to detect an unobstructed glutamate signal at 3 T that is resolved from glutamine and NAA at 2.35 ppm. TE-Averaged PRESS therefore provides an unambiguous measurement of glutamate as well as other metabolites such as NAA, choline, creatine, and myo-inositol. In this study, we extend the single voxel TE-Averaged PRESS technique for two-dimensional (2D) spectroscopic imaging (TE-Averaged MRSI) to generate 2D glutamate maps. To facilitate TE-Averaged MRSI within a reasonable time, a fast encoding trajectory was used. This enabled rapid acquisition of TE-Averaged spectral arrays with good spectral bandwidth (977 Hz) and resolution (approximately 2 Hz). MRSI data arrays of 10 x 16 were acquired with 1.8 cm3 spatial resolution over a approximately 110 cm3 volume in a scan time of approximately 21 min. Two-dimensional metabolite maps were obtained with good SNR and clear differentiation in glutamate levels was observed between gray and white matter with significantly higher glutamate in gray matter relative to white matter as anticipated.

Myo-inositol is a strongly coupled system and resonates at four chemical shift positions. At 1.5 T, only the singlet component at 3.57 ppm is detected. However, at 3 T this resonance is resolved into its components at 3.55 ppm and 3.61 ppm. Due to the increased spectral resolution and signal-to-noise ratio, it is anticipated that the quantification of myo-inositol should improve at 3 T. Using data from normal controls and the LCmodel quantification procedure, we found that the quantification precision, reproducibility and detection sensitivity of myo-inositol is significantly better at 3 T relative to 1.5 T.

An accurate measurement of the transverse relaxation time T2, and the histogram of T2 in the brain parenchyma can be accomplished in vivo using a multi-echo magnetic resonance imaging sequence. An estimate of the error in the T2 measurement is derived using copper sulfate doped water phantoms. Correction factors are calculated and applied to the signal intensity of each voxel prior to the in vivo T 2 evaluation. These corrected T2 are in good agreement with the theoretical values calculated from copper sulfate concentrations. This technique is then applied to calculate T2 histograms of the brain. The population studied was composed of normal volunteers and multiple sclerosis patients. The corrected T 2 histogram method discriminates the normal control population from the MS population, and also discriminates between relapsing-remitting patients and primary progressive or secondary progressive patients. Moreover using this approach we are able to detect in MS patients a global shift of the T2 of the white mater toward higher values. The results of this study showed that the method is easy to implement and may be used to characterize MS pathology. © 2002 Elsevier Science Inc. All rights reserved.

Although there are trends in the morphologic, metabolic, hemodynamic, and structural properties of untreated gliomas that are reflected in MR measurements, there is considerable heterogeneity both within and between lesions of the same histologic grade. The spatial extent of the abnormality in ADC and RA images is similar to the T2 lesion, but there is no obvious difference in intensity between grades. The rCBV is significantly increased in the enhancing volume of grade 4 lesions but is similar or reduced in intensity for most grade 3 lesions. There are clear differences between the enhancing volumes and the regions with increased Cho that may be highly significant for planning focal therapy. The location and intensity of the Lac/Lip peaks are consistent with those representing regions of necrosis for grade 4 lesions. The fact that small Lac/Lip peaks can also be seen in grade 2 and grade 3 lesions suggests that their presence may be indicative of regions that are likely to progress to a higher grade. If this were the case, it would be valuable for directing biopsies. The correlations between rCBV, Cho, and ADC suggest that cellularity, membrane turnover, and vascularity are linked in grade 4 lesions. It is not clear whether there is any relationship between these parameters regions in grade 2 or grade 3 gliomas. While further work is required to optimize the methodology associated with these MR parameters, it seems likely that combining the information from such measurements may be valuable for predicting outcome and tailoring therapy to individual patients.

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups. Explicit memory as well as perceptual and conceptual implicit memory were examined using free recall, word fragment completion, and exemplar generation tests, respectively. All three groups of MS patients exhibited free recall deficits and normal priming on the exemplar generation test. However, the PPMS group exhibited a deficit in word fragment completion priming, whereas the RRMS and SPMS groups exhibited normal levels of priming on this task. Lesion load was assessed using magnetic resonance imaging and was negatively correlated with explicit memory performance, but it did not account for the observed deficits in perceptual implicit memory. The results indicate that PPMS patients exhibit a pattern of memory impairment that is distinct from that of the RRMS and SPMS groups. Moreover, the results indicate that perceptual implicit memory can be neurologically dissociated from conceptual implicit memory.

Purpose: The role of radiotherapy (RT) seems established for patients with low-grade gliomas with poor prognostic factors. Three-dimensional (3D) magnetic resonance spectroscopy imaging (MRSI) has been reported to be of value in defining the extent of glioma infiltration. We performed a study examining the impact MRSI would have on the routine addition of 2–3-cm margins around MRI T2-weighted hyperintensity to generate the treatment planning clinical target volume (CTV) for low-grade gliomas. Methods and Materials: Twenty patients with supratentorial gliomas WHO Grade II (7 astrocytomas, 6 oligoastrocytomas, 7 oligodendrogliomas) underwent MRI and MRSI before surgery. The MRI was contoured manually; the regions of interest included T2 hyperintensity and, if present, regions of contrast enhancement on T1-weighted images. The 3D-MRSI peak parameters for choline and N -acetyl-aspartate, acquired voxel-by-voxel, were categorized using a choline/ N -acetyl-aspartate index (CNI), a tool for quantitative assessment of tissue metabolite levels, with CNI 2 being the lowest value corresponding to tumor. CNI data were aligned to MRI and displayed as 3D contours. The relationship between the anatomic and metabolic information on tumor extent was assessed by comparing the CNI contours and other MRSI-derived metabolites to the MRI T2 volume. Results: The limitations in the size of the region "excited" meant that MRSI could be used to evaluate only a median 68% of the T2 volume (range 38–100%), leaving the volume T2c. The CNI 2 volume (median 29 cm 3 , range 10–73) was contained totally within the T2c in 55% of patients. In the remaining patients, the volume of CNI 2 extending beyond the T2c was quite small (median 2.3 cm 3 , range 1.4–5.2), but was not distributed uniformly about the T2c, extending up to 22 mm beyond it. Two patients demonstrated small regions of contrast enhancement corresponding to the regions of highest CNI. Other metabolites, such as creatine and lactate, seem useful for determining less and more radioresistant areas, respectively. Conclusion: Metabolically active tumor, as detected by MRSI, is restricted mainly to the T2 hyperintensity in low-grade gliomas, but can extend outside it in a limited and nonuniform fashion up to 2 cm. Therefore, a CTV including T2 and areas of CNI extension beyond the T2 hyperintensity would result in a reduction in the size and a change in the shape of the standard clinical target volumes generated by adding uniform margins of 2–3 cm to the T2 hyperintensity.

Purpose: Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a reliable indicator of active and microscopic disease in malignant brain tumors. We assessed the impact MRSI might have on the target volumes used for radiation therapy treatment planning for high-grade gliomas. Methods and Materials: Thirty-four patients (22 Grade III; 12 Grade IV astrocytomas) were evaluated; each had undergone MRI and MRSI studies before surgery. MRI data sets were contoured for T1 region of contrast enhancement (T1), region of necrosis, and T2 region of hyperintensity (T2). The three-dimensional MRSI peak parameters for choline (Cho) and N -acetylaspartate (NAA), acquired by a multivoxel technique, were categorized based on an abnormality index (AI), a quantitative assessment of tissue metabolite levels. The AI data were aligned to the MRI and displayed as three-dimensional contours. AI vs. T conjoint and disjoint volumes were compared. Results: For both grades, although T2 estimated the region at risk of microscopic disease as being as much as 50% greater than by MRSI, metabolically active tumor still extended outside the T2 region in 88% of patients by as many as 28 mm. In addition, T1 suggested a lesser volume and different location of active disease compared to MRSI. Conclusion: The use of MRSI to define target volumes for RT treatment planning would increase, and change the location of, the volume receiving a boost dose as well as reduce the volume receiving a standard dose. Incorporation of MRSI into the treatment-planning process may have the potential to improve control while reducing complications.

Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy.

Objectives . To assess and compare the clinical usefulness of transrectal ultrasound (TRUS), magnetic resonanceimaging (MRI), and three-dimensional proton magnetic resonance spectroscopic imaging (3-D MRSI) in detecting local recurrence of carcinoma of the prostate (CaP) in patients with detectable prostate-specific antigen (PSA) levels after cryosurgery. Methods . In a prospective study, 25 patients who had undergone cryosurgery as primary treatment for CaPunderwent endorectal MRI and 3-D MRSI, followed by TRUS-guided prostate biopsy. At the time of study, 20 patients had detectable PSA; the remaining 5 patients served as controls. All patients had random sextant and guided prostate biopsy for correlation with imaging and MR spectroscopic findings. Results . In patients with detectable PSA, MRSI identified, location-for-location, all foci of CaP and benign prostatic tissue that were detected by prostate biopsy. MRSI identified more sites with CaP than did prostate biopsy, indicating a larger volume of cancer. In 2 patients with detectable PSA and negative prostate biopsy, MRSI identified 11 voxels with viable prostatic tissue. In patients with undetectable PSA, both MRSI and prostate biopsy showed necrosis. Ultrasound and MRI were very poor tools for identifying recurrent cancer and differentiating between viable and necrotic prostate tissue. Conclusions . 3-D MRSI is superior to TRUS and MRI in differentiating among CaP, BPH, and necrosis when local recurrence after cryosurgery is suspected. By providing chemical mapping of the prostate in contiguous voxels, the addition of spectroscopy to endorectal MRI increases the sensitivity for detection of local recurrence.

previously reported improvement in PFS (10.4 vs. 4.0 years, p Z 0.002; HR Z 0.50). Treatment arm was identified as a prognostic variable in favor of RT + PCV for both OS (p Z 0.003; HR Z 0.59) and PFS (p < 0.001; HR Z 0.49). Histology was prognostic for OS (p < 0.001; HR Z 2.16) and PFS (p < 0.001; HR Z 1.85) in favor of O compared to A. Male gender was prognostic for inferior OS (p Z 0.02; HR Z 1.51). Molecular markers were not pre-specified; post-hoc analysis of these is ongoing. Conclusions: For “high-risk” LGG, defined as age < 40 years with subtotal resection/biopsy or 40 years with any degree of resection, RT followed by 6 cycles of PCV prolongs both OS and PFS, and RT plus chemotherapy should therefore be considered a new standard of care for such patients. Astrocytic histology and male gender predict for poorer survival. Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). Author Disclosure: M.P. Mehta: E. Research Grant; Novocure. F. Honoraria; Research to Excellence, Soreno Foundation. G. Consultant; Abbvie, BMS, Elekta, Merck, Novocure, Novelos, Phillips. I. Travel Expenses; Abbvie, Celldex, Elekta, Phillips, Roche. K. Advisory Board; Celldex, Roche. N. Stock Options; Pharmacyclics, Accuray. P. Royalty; Demos. S. Leadership; RTOG. M. Won: None. E.G. Shaw: None. J. Buckner: None. M. Gilbert: E. Research Grant; Merck, Genentech, GSK. F. Honoraria; Genentech, Merck. K. Advisory Board; Merck, Genentech, BMS, Abbvie, EMD Serono. G. Barger: None. S. Coons: None. P. Ricci: None. D. Bullard: None. P.D. Brown: None. K. Stelzer: None. D.G. Brachman: None. J.H. Suh: G. Consultant; Varian. C. Schultz: None. J. Bahary: None. B.J. Fisher: None. H. Kim: None. A.D. Murtha: None. W.J. Curran: S. Leadership; RTOG.

A technique for processing noisy 1-D spectra is described. Unlike standard filters designed merely for noise suppression, this technique both smooths and automatically quantifies the peaks in a spectrum. There are three stages involved; identification of peaks from slowly varying background and random noise, estimation of peak parameters, and finally smoothing of the peaks on an individual basis. Simulated spectra, representative of those obtained from biological samples, are used to test the performance of the technique. The results agree very well with theoretical predictions. Finally, a comparison is made with the performance of two filters used for noise suppression, the matched filter and the maximum entropy method. The technique has considerable advantages over these two methods for the type of spectra considered here, the most important in practical terms being the ability to obtain automatic estimates of peak parameters together with a clear definition of the accuracy of these estimates.

The ability to produce accurate estimates of peak parameters in 1 D NMR spectra is of critical importance in interpreting experimental results, particularly for the analysis of in vivo spectra, where low signal to noise is common. The accuracy of the quantification obtainable using the automatic algorithm PIQABLE is reported here. The original version of PIQABLE produces reliable estimates of the areas of isolated peaks in low signal-to-noise spectra with a variable baseline. The algorithm has been extended to treat partially overlapping peaks and automatically estimate constant and linear phase corrections. A variety of simulated spectra has been analyzed in order to address four different topics: the accuracy of area estimates as a function of peak signal-to-noise ratio, the influence of variable baseline on area estimates, the effect of partially overlapping peaks, and the performance of the automatic phasing routines. The results underline the limitations imposed on any quantification method by the magnitude of random noise in the spectrum and the importance of employing statistical techniques to identify peaks and predict the accuracy of parameter estimates.