Sodium Magnetic Resonance Imaging Research Articles

Variability of CubeQuant T1ρ, quantitative DESS T2, and cones sodium MRI in knee cartilage

To measure the variability of T1ρ relaxation times using CubeQuant, T2 relaxation times using quantitative double echo in steady state (DESS), and normalized sodium signals using 3D cones sodium magnetic resonance imaging (MRI) of knee cartilage in vivo at 3 T. Eight healthy subjects were scanned at 3 T at baseline, 1 day, 5 months, and 1 year. Ten regions of interest (ROIs) of knee cartilage were segmented in the medial and lateral compartments of each subject's knee. T1ρ and T2 relaxation times and normalized sodium signals were measured and the root-mean-square coefficient of variation (CVRMS) was calculated. Intra-subject variability was measured over short, moderate and long-term, as well as intra-observer and inter-observer variability. The average intra-subject CVRMS measurements over short, moderate, and long-term time periods were 4.6%, 6.1%, and 6.0% for the T1ρ measurements, 6.4%, 9.3%, and 10.7% for the T2 measurements and 11.3%, 11.6%, and 12.9% for the sodium measurements, respectively. The average CVRMS measurements for intra-observer and inter-observer segmentation were 3.8% and 5.7% for the T1ρ measurements, 4.7% and 6.7% for the T2 measurements, and 8.1% and 11.4% for the sodium measurements, respectively. These CVRMS measurements are substantially lower than previously measured changes expected in patients with advanced osteoarthritis compared to healthy volunteers, suggesting that CubeQuant T1ρ, quantitative DESS T2 and 3D cones sodium measurements are sufficiently sensitive for in vivo cartilage studies.

Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis

Hyponatraemia in cirrhosis is associated with impaired cognition and poor health-related quality of life (HRQOL). However, the benefit of hyponatraemia correction is unclear. The aim of this study was to evaluate the effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics with hyponatraemia. Cirrhotics with Na <130 mEq/L were included for a four-week trial. At screening, patients underwent cognitive and HRQOL testing, serum/urine chemistries and companion burden assessment. Patients then underwent fluid restriction and diuretic withdrawal for two weeks after which cognitive tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging (MRI) was performed and tolvaptan was initiated for 14 days with frequent clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were repeated. Comparisons were made between screen, pre-and post-drug periods Na, urine/serum laboratories, cognition, HRQOL and companion burden. 24 cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement in cognition. The remaining 17 received tolvaptan of which 14 completed the study over 13 ± 2 days (age 58 ± 6 years, MELD 17, 55% HCV, median 26 mg/day of tolvaptan). Serum Na and urine free water clearance increased with tolvaptan without changes in mental status or liver function. Cognitive function, HRQOL and companion burden only improved in these 14 patients after tolvaptan, along with reduced total brain and white matter volume, increase in choline on magnetic resonance spectroscopy, and reduced cytotoxic oedema. Short-term tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is associated with cognitive, HRQOL, brain MRI and companion burden improvement.

A method for estimating intracellular sodium concentration and extracellular volume fraction in brain in vivo using sodium magnetic resonance imaging.

In this feasibility study we propose a method based on sodium magnetic resonance imaging (MRI) for estimating simultaneously the intracellular sodium concentration (C1, in mM) and the extracellular volume fraction (α) in grey and white matters (GM, WM) in brain in vivo. Mean C1 over five healthy volunteers was measured ~11 mM in both GM and WM, mean α was measured ~0.22 in GM and ~0.18 in WM, which are in close agreement with standard values for healthy brain tissue (C1 ~ 10–15 mM, α ~ 0.2). Simulation of ‘fluid’ and ‘solid’ inclusions were accurately detected on both the C1 and α 3D maps and in the C1 and α distributions over whole GM and WM. This non-invasive and quantitative method could provide new biochemical information for assessing ion homeostasis and cell integrity in brain and help the diagnosis of early signs of neuropathologies such as multiple sclerosis, Alzheimer's disease, brain tumors or stroke.

In vivo double quantum filtered sodium magnetic resonance imaging of human brain

Sodium signal from ordered environments can be selectively detected using a double-quantum magic angle (DQ-MA) sequence. This study presents the first DQ-MA sodium images of the human brain and evaluates the effect of preparation time (τ) on the signal. Three phantoms of saline, agar gel, and xanthan gum were used to test the correct functioning of the DQ-MA sequence. Five healthy volunteers were imaged using DQ-MA with varying τ to determine the optimal preparation time. DQ-MA images were acquired with 1 or 2 averages and nominal resolution of 15 mm isotropic in 3.5 or 7 min, respectively. In addition, higher nominal resolution (8.4 mm isotropic) DQ-MA images were acquired from another subject in 48 min. Post hoc simulations were performed to explain the effect of τ on imaging results. The DQ-MA sequence generates signal from only the xanthan gum phantom, correctly suppressing signal from environments in which the time-averaged quadrupolar interaction is expected to be zero (saline, agar). This sequence generates signal throughout the brain with maximum detection when τ=3 ms. The existence of DQ-MA signal in the human brain indicates the presence of sodium nuclei in ordered environments and provides a novel contrast mechanism.

Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10

Evaluation of cancer-therapy efficacy at early time points is necessary for realizing the goal of delivering maximally effective treatment. Molecular imaging with carefully selected tracers and methodologies can provide the means for realizing this ability. Many therapies are aimed at inducing apoptosis in malignant tissue; thus, the ability to quantify apoptosis in vivo may be a fruitful approach. Apoptosis rate changes occur on a fast time scale, potentially allowing correspondingly rapid decisions regarding therapy value. However, quantification of tissue status based on apoptosis imaging is complicated by this time scale and by the spatial heterogeneity of the process. Using the positron emission tomography (PET) tracer 2-(5-fluoro-pentyl)-2-methyl-malonic acid (F-18 ML-10), we present methods of voxelwise analysis yielding quantitative measures of apoptosis changes, parametric apoptosis change images, and graphical representation of apoptotic features. A method of deformable registration to account for anatomic changes between scan time points is also demonstrated. Overall apoptotic rates deduced from imaging depend on tumor density and the specific rate of apoptosis, a situation resulting in an ambiguity in the source of observed image-based changes. The ambiguity may be resolved through multimodality imaging. An example of intracellular sodium magnetic resonance imaging coupled with F-18 ML-10 PET is provided.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

SODIUM ACCUMULATION IS ASSOCIATED WITH DISABILITY AND PROGRESSION IN MULTIPLE SCLEROSIS: A 23NA MRI STUDY

IntroductionNeuroaxonal loss is the major pathological substrate of irreversible disability in Multiple Sclerosis (MS). Sodium is maintained at lower concentration within the intra–axonal space by the Na/K/ATPase pump. In MS,...

T1-Weighted Sodium MRI of the Articulator Cartilage in Osteoarthritis: A Cross Sectional and Longitudinal Study

Structural magnetic resonance imaging (MRI) has shown great utility in diagnosing soft tissue burden in osteoarthritis (OA), though MRI measures of cartilage integrity have proven more elusive. Sodium MRI can reflect the proteoglycan content of cartilage; however, it requires specialized hardware, acquisition sequences, and long imaging times. This study was designed to assess the potential of a clinically feasible sodium MRI acquisition to detect differences in the knee cartilage of subjects with OA versus healthy controls (HC), and to determine whether longitudinal changes in sodium content are observed at 3 and 6 months. 28 subjects with primary knee OA and 19 HC subjects age and gender matched were enrolled in this ethically-approved study. At baseline, 3 and 6 months subjects underwent structural MRI and a 0.4ms echo time 3D T1-weighted sodium scan as well as the knee injury and osteoarthritis outcome score (KOOS) and knee pain by visual analogue score (VAS). A standing radiograph of the knee was taken for Kellgren-Lawrence (K-L) scoring. A blinded reader outlined the cartilage on the structural images which was used to determine median T1-weighted sodium concentrations in each region of interest on the co-registered sodium scans. VAS, K-L, and KOOS all significantly separated the OA and HC groups. OA subjects had higher T1-weighted sodium concentrations, most strongly observed in the lateral tibial, lateral femoral and medial patella ROIs. There were no significant changes in cartilage volume or sodium concentration over 6 months. This study has shown that a clinically-feasible sodium MRI at a moderate 3T field strength and imaging time with fluid attenuation by T1 weighting significantly separated HCs from OA subjects.

Sodium (23Na) ultra-short echo time imaging in the human brain using a 3D-Cones trajectory

ObjectSodium magnetic resonance imaging (23Na-MRI) of the brain has shown changes in 23Na signal as a hallmark of various neurological diseases such as stroke, Alzheimer’s disease, Multiple Sclerosis and Huntington’s disease. To improve scan times and image quality, we have implemented the 3D-Cones (CN) sequence for in vivo 23Na brain MRI.Materials and methodsUsing signal-to-noise (SNR) as a measurement of sequence performance, CN is compared against more established 3D-radial k-space sampling schemes featuring cylindrical stack-of-stars (SOS) and 3D-spokes kooshball (KB) trajectories, on five healthy volunteers in a clinical setting. Resolution was evaluated by simulating the point-spread-functions (PSFs) and experimental measures on a phantom.ResultsAll sequences were shown to have a similar SNR arbitrary units (AU) of 6–6.5 in brain white matter, 7–9 in gray matter and 17–18 AU in cerebrospinal fluid. SNR between white and gray matter were significantly different for KB and CN (p = 0.046 and <0.001 respectively), but not for SOS (p = 0.1). Group mean standard deviations were significantly smaller for CN (p = 0.016). Theoretical full-width at half-maximum linewidth of the PSF for CN is broadened by only 0.1, compared to 0.3 and 0.8 pixels for SOS and KB respectively. Actual image resolution is estimated as 8, 9 and 6.3 mm for SOS, KB and CN respectively.ConclusionThe CN sequence provides stronger tissue contrast than both SOS and KB, with more reproducible SNR measurements compared to KB. For CN, a higher true resolution in the same amount of time with no significant trade-off in SNR is achieved. CN is therefore more suitable for 23Na-MRI in the brain.

Sodium accumulation is associated with disability and a progressive course in multiple sclerosis

Neuroaxonal loss is a major substrate of irreversible disability in multiple sclerosis, however, its cause is not understood. In multiple sclerosis there may be intracellular sodium accumulation due to neuroaxonal metabolic dysfunction, and increased extracellular sodium due to expansion of the extracellular space secondary to neuroaxonal loss. Sodium magnetic resonance imaging measures total sodium concentration in the brain, and could investigate this neuroaxonal dysfunction and loss in vivo. Sodium magnetic resonance imaging has been examined in small cohorts with relapsing-remitting multiple sclerosis, but has not been investigated in patients with a progressive course and high levels of disability. We performed sodium magnetic resonance imaging in 27 healthy control subjects, 27 patients with relapsing-remitting, 23 with secondary-progressive and 20 with primary-progressive multiple sclerosis. Cortical sodium concentrations were significantly higher in all subgroups of multiple sclerosis compared with controls, and deep grey and normal appearing white matter sodium concentrations were higher in primary and secondary-progressive multiple sclerosis. Sodium concentrations were higher in secondary-progressive compared with relapsing-remitting multiple sclerosis in cortical grey matter (41.3 ± 4.2 mM versus 38.5 ± 2.8 mM, P = 0.008), normal appearing white matter (36.1 ± 3.5 mM versus 33.6 ± 2.5 mM, P = 0.018) and deep grey matter (38.1 ± 3.1 mM versus 35.7 ± 2.4 mM, P = 0.02). Higher sodium concentrations were seen in T₁ isointense (44.6 ± 7.2 mM) and T1 hypointense lesions (46.8 ± 8.3 mM) compared with normal appearing white matter (34.9 ± 3.3 mM, P < 0.001 for both comparisons). Higher sodium concentration was observed in T₁ hypointense lesions in secondary-progressive (49.0 ± 7.0 mM) and primary-progressive (49.3 ± 8.0 mM) compared with relapsing-remitting multiple sclerosis (43.0 ± 8.5 mM, P = 0.029 for both comparisons). Independent association was seen of deep grey matter sodium concentration with expanded disability status score (coefficient = 0.24, P = 0.003) and timed 25 ft walk speed (coefficient = -0.24, P = 0.01), and of T1 lesion sodium concentration with the z-scores of the nine hole peg test (coefficient = -0.12, P < 0.001) and paced auditory serial addition test (coefficient = -0.081, P < 0.001). Sodium concentration is increased within lesions, normal appearing white matter and cortical and deep grey matter in multiple sclerosis, with higher concentrations seen in secondary-progressive multiple sclerosis and in patients with greater disability. Increased total sodium concentration is likely to reflect neuroaxonal pathophysiology leading to clinical progression and increased disability.

Biomedical applications of sodium MRI in vivo

In this article we present an up-to-date overview of the potential biomedical applications of sodium magnetic resonance imaging (MRI) in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle, and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: 1) the role of sodium in biological tissues, 2) a short review on sodium magnetic resonance, and 3) a review of some studies on sodium MRI on different organs/diseases to date.

Variability of Apoptosis and Response in N1-S1 Rodent Hepatomas to Benzamide Riboside and Correlation to Early Changes in Water Apparent Diffusion Coefficient and Sodium MR Imaging

PurposeThis pilot trial assesses variability of apoptosis and response 1 day after hepatic intraarterial (IA) benzamide riboside (BR) in rodent hepatomas and its correlation to water apparent diffusion coefficient (ADC) and single-quantum (SQ) and triple-quantum–filtered (TQF) sodium-23 (23Na) magnetic resonance (MR) imaging. Materials and MethodsSprague–Dawley rats (n = 8) were inoculated with 106 N1-S1 cells. IA BR (20 mg/kg) was infused after 14 days. Animals were killed 1 day (n = 4) or 21 days (n = 4) after therapy. Imaging was performed 1 day before and after treatment. Volume was assessed over 2 weeks. Percentage apoptosis was counted from terminal deoxynucleotidyl transferase dUTP nick-end labeling–stained slides at 400×magnification. Kruskal–Wallis tests were used to compare apoptosis, and Wilcoxon signed-rank tests were used to compare MR signal intensity (SI). ResultsApoptosis was marginally greater in tumor than in nontumor (6.7% vs 1.3%; P = .08), varying from 2% to 10%. Before treatment, MR SI was greater in tumor than in nontumor (ADC, 1.18 vs 0.76 [P = .0078]; SQ, 1.20 vs 1.04 [P = .03]; TQF, 0.55 vs 0.34 [P = .03]). After treatment, tumors increased in volume (0.62 vs 0.33; P = .016) variably over 2 weeks. MR SI remained greater in tumor than in nontumor (ADC, 1.20 vs 0.77 [P = .0078]; SQ, 1.76 vs 1.15 [P = .016]; TQF, 0.84 vs 0.49 [P = .03]). SQ and TQF SI increased by 47% (P = .016) and 53% (P = .016) in tumors, whereas ADC did not change. ConclusionsApoptosis was marginal and varied from 2% to 10%. Water ADC, SQ, and TQF MR imaging distinguished tumor from nontumor. Changes in water ADC and sodium MR imaging correlated to apoptosis and volume in select cases, but additional animals are needed to validate this trend against tumor growth.

Articular Cartilage: Evaluation with Fluid-suppressed 7.0-T Sodium MR Imaging in Subjects with and Subjects without Osteoarthritis

To assess the potential use of sodium magnetic resonance (MR) imaging of cartilage, with and without fluid suppression by using an adiabatic pulse, for classifying subjects with versus subjects without osteoarthritis at 7.0 T. The study was approved by the institutional review board and was compliant with HIPAA. The knee cartilage of 19 asymptomatic (control subjects) and 28 symptomatic (osteoarthritis patients) subjects underwent 7.0-T sodium MR imaging with use of two different sequences: one without fluid suppression (radial three-dimensional sequence) and one with fluid suppression (inversion recovery [IR] wideband uniform rate and smooth truncation [WURST]). Fluid suppression was obtained by using IR with an adiabatic inversion pulse (WURST pulse). Mean sodium concentrations and their standard deviations were measured in the patellar, femorotibial medial, and lateral cartilage regions over four consecutive sections for each subject. The minimum, maximum, median, and average means and standard deviations were calculated over all measurements for each subject. The utility of these measures in the detection of osteoarthritis was evaluated by using logistic regression and the area under the receiver operating characteristic curve (AUC). Bonferroni correction was applied to the P values obtained with logistic regression. Measurements from IR WURST were found to be significant predicators of all osteoarthritis (Kellgren-Lawrence score of 1-4) and early osteoarthritis (Kellgren-Lawrence score of 1 or 2). The minimum standard deviation provided the highest AUC (0.83) with the highest accuracy (>78%), sensitivity (>82%), and specificity (>74%) for both all osteoarthritis and early osteoarthritis groups. Quantitative sodium MR imaging at 7.0 T with fluid suppression by using adiabatic IR is a potential biomarker for osteoarthritis.

Sodium quantification in the spinal cord at 3T

Sodium channels are involved in neuronal function and therefore methods to assess tissue sodium concentration in vivo are exceptionally appealing. Recently there has been a renewed interest for brain sodium magnetic resonance imaging (MRI), thanks to higher magnetic field strength scanners. However, sodium measures in the spinal cord are lacking due to major technical challenges. Here we propose for the first time a clinically feasible non-invasive method for quantifying sodium in the spine using magnetic resonance spectroscopy. Sodium spectra from the cervical cord were collected using image selected in vivo spectroscopy (∼14 min scan time) and quantified using a reference phantom. The sodium magnetic resonance spectroscopy measures provided in vivo concentration estimates of 31.2±2.4 mM. Repeat scans showed good reproducibility with a coefficient of variation of <6%. Proposed here for the first time is a fast non-invasive technique to quantify total sodium in the spinal cord in vivo. This newly proposed technique has a great potential for translation into clinic, thanks to its simplicity.

Rapid computation of sodium bioscales using gpu‐accelerated image reconstruction

AbstractQuantitative sodium magnetic resonance imaging permits noninvasive measurement of the tissue sodium concentration (TSC) bioscale in the brain. Computing the TSC bioscale requires reconstructing and combining multiple datasets acquired with a non‐Cartesian acquisition that highly oversamples the center of k‐space. Even with an optimized implementation of the algorithm to compute TSC, the overall processing time exceeds the time required to collect data from the human subject. Such a mismatch presents a challenge for sustained sodium imaging to avoid a growing data backlog and provide timely results. The most computationally intensive portions of the TSC calculation have been identified and accelerated using a consumer graphics processing unit (GPU) in addition to a conventional central processing unit (CPU). A recently developed data organization technique called Compact Binning was used along with several existing algorithmic techniques to maximize the scalability and performance of these computationally intensive operations. The resulting GPU+CPU TSC bioscale calculation is more than 15 times faster than a CPU‐only implementation when processing 256 × 256 × 256 data and 2.4 times faster when processing 128 × 128 × 128 data. This eliminates the possibility of a data backlog for quantitative sodium imaging. The accelerated quantification technique is suitable for general three‐dimensional non‐Cartesian acquisitions and may enable more sophisticated imaging techniques that acquire even more data to be used for quantitative sodium imaging. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 29–35, 2013.

Sodium MR Imaging of the Lumbar Intervertebral Disk at 7 T: Correlation with T2 Mapping and Modified Pfirrmann Score at 3 T—Preliminary Results

To compare sodium imaging of lumbar intervertebral disks in asymptomatic volunteers at 7-T magnetic resonance (MR) imaging with quantitative T2 mapping and morphologic scoring at 3 T. Following ethical board approval and informed consent, the L2-3 to L5-S1 disks were examined in 10 asymptomatic volunteers (nine men, one woman; mean age, 30 years; range, 23-43 years). At 7 T, normalized sodium signal-to-noise ratios were calculated, by using region-of-interest analysis. At 3 T, T2 mapping was performed with a multiecho spin-echo sequence (repetition time msec/echo times msec, 1500/24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156). T2 values were calculated over the nucleus, with a pixelwise, monoexponential nonnegative least-squares-fit analysis. Morphologic grading according to a modified Pfirrmann score was assessed independently by three experienced musculoskeletal radiologists, and Pearson correlation analysis of the covariates was performed. The mean normalized sodium signal intensity was 275.5±115.4 (standard deviation). The T2 mapping showed a mean value of 89.8 msec±19.34. The median modified Pfirrmann score was 2b (90% had score≤3c). The Pearson correlation coefficient showed a cubic function between sodium imaging and the modified Pfirrmann score, a moderate inverse correlation between T2 mapping and the modified Pfirrmann score (r=-0.62), and no correlation between sodium imaging and T2 mapping (r=0.06). The results suggest that MR imaging of the intervertebral disk, using sodium imaging and T2 mapping, can help characterize different component changes and that both of these methods are to some degree related to the Pfirrmann score.

Part 1

Development of a dual-tuned proton/sodium radiofrequency (RF) coil for magnetic resonance imaging (MRI) of the rabbit spine and quantification of sodium concentration in intervertebral discs. To develop the dual-tuned proton/sodium MRI of rabbit lumbar spine to investigate proteoglycan matrix content and intervertebral disc degeneration (IDD). IDD is a common chronic condition that may lead to back pain, limited activity, and disability. Early-stage IDD involves the loss of proteoglycan matrix and water content in the disc. Sodium MRI is a promising noninvasive technique for quantitative measurement of proteoglycan changes associated with IDD. The combined structural (proton) and biochemical (sodium) MRI facilitates the investigation of morphological and molecular changes associated with degeneration of discs. Multichannel dual-tuned proton/sodium transceiver RF coil of the rabbit spine was developed and optimized at 3T human scanner-8 channels allocated for the sodium coil and 4 channels for the proton coil. High-resolution anatomy proton images of the discs were acquired using turbo spin echo and dual echo steady state sequence. Sodium concentration of the discs was quantified from sodium magnetic resonance (MR) images that were calibrated for signal attenuation because of RF field inhomogeneity, sodium MR relaxation times, and disc thickness. Twelve rabbits (~1-yr old, female, 5.2 ± 0.4 kg) were used for measuring disc sodium concentration. High-resolution in vivo proton and sodium MR images of rabbit discs (≤2-mm thickness) were successfully obtained using an in-house dual-tuned proton/sodium RF coil at 3T. The total acquisition time for each set of images was approximately 40 minutes. Sodium concentration of normal rabbit lumbar discs was measured at 269.7 ± 6.3 mM, and this measurement was highly reproducible, with 5.3% of coefficient of variation. Sodium concentrations of rabbit lumbar discs were reliably measured using our newly developed dual-tuned multichannel proton/sodium RF coil at 3T.

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [18F]fluorothymidine (F-18 FLT) PET, sodium (23Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked.While both modalities independently show a change in tissue status as a function of scan time point, results illustrate that the two modalities may provide complementary information regarding tumor progression and response. Additionally, tumor status changes were found to vary in different regions of tumor. The degree to which these methods are useful for GBM therapy response assessment and particularly for differentiating true progression from pseudoprogression requires additional patient data and correlation of these imaging biomarker changes with clinical outcome.

Comparing anisotropic diffusion filters for the enhancement of sodium magnetic resonance images

The anisotropic diffusion (AND) filter, an image processing technique derived from physics, was applied to low-resolution sodium magnetic resonance imaging (MRI) to examine the possibilities of image enhancement by postprocessing. We compared six different variants of AND filters. Besides the qualitative good results on phantom measurements, quantitative analyses on MRI of human kidney yielded major improvements in noise reduction and other quality measures: the noise (i.e., the standard deviation in the image background) could be reduced to 1%–2% of its original value, while linear filters (Gaussian, Fermi, Hamming) achieved a reduction to 42%–64%. Besides that, less than 5% of structures and intensities are lost when using AND filters. Comparing the different variants, the two-dimensional and the three-dimensional AND filter outperformed the histogram-of-gradient and tensor-based AND filter. We envision that by using these AND filters, quantitative analysis of sodium MRI of kidney could be improved.

Distribution of Brain Sodium Accumulation Correlates with Disability in Multiple Sclerosis: A Cross-sectional23Na MR Imaging Study

To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.