Manoj K. Sarma

MR spectroscopic imaging and diffusion-weighted imaging of prostate cancer with Gleason scores

To investigate functional changes in prostate cancer patients with three pathologically proven different Gleason scores (GS) (3+3, 3+4, and 4+3) using magnetic resonance spectroscopic imaging (MRSI) and diffusion‐weighted imaging (DWI).

Regional brain gray and white matter changes in perinatally HIV-infected adolescents

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C

Objective: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. Method: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI. Results: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV− controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV− controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance. Conclusions: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

Accelerated Echo-Planar J-Resolved Spectroscopic Imaging in the Human Brain Using Compressed Sensing: A Pilot Validation in Obstructive Sleep Apnea

BACKGROUND AND PURPOSE: Echo-planar J-resolved spectroscopic imaging is a fast spectroscopic technique to record the biochemical information in multiple regions of the brain, but for clinical applications, time is still a constraint. Investigations of neural injury in obstructive sleep apnea have revealed structural changes in the brain, but determining the neurochemical changes requires more detailed measurements across multiple brain regions, demonstrating a need for faster echo-planar J-resolved spectroscopic imaging. Hence, we have extended the compressed sensing reconstruction of prospectively undersampled 4D echo-planar J-resolved spectroscopic imaging to investigate metabolic changes in multiple brain locations of patients with obstructive sleep apnea and healthy controls. MATERIALS AND METHODS: Nonuniform undersampling was imposed along 1 spatial and 1 spectral dimension of 4D echo-planar J-resolved spectroscopic imaging, and test-retest reliability of the compressed sensing reconstruction of the nonuniform undersampling data was tested by using a brain phantom. In addition, 9 patients with obstructive sleep apnea and 11 healthy controls were investigated by using a 3T MR imaging/MR spectroscopy scanner. RESULTS: Significantly reduced metabolite differences were observed between patients with obstructive sleep apnea and healthy controls in multiple brain regions: NAA/Cr in the left hippocampus; total Cho/Cr and Glx/Cr in the right hippocampus; total NAA/Cr, taurine/Cr, scyllo-Inositol/Cr, phosphocholine/Cr, and total Cho/Cr in the occipital gray matter; total NAA/Cr and NAA/Cr in the medial frontal white matter; and taurine/Cr and total Cho/Cr in the left frontal white matter regions. CONCLUSIONS: The 4D echo-planar J-resolved spectroscopic imaging technique using the nonuniform undersampling–based acquisition and compressed sensing reconstruction in patients with obstructive sleep apnea and healthy brain is feasible in a clinically suitable time. In addition to brain metabolite changes previously reported by 1D MR spectroscopy, our results show changes of additional metabolites in patients with obstructive sleep apnea compared with healthy controls.

Multidimensional MR spectroscopic imaging of prostate cancer in vivo

Prostate cancer (PCa) is the second most common type of cancer among men in the United States. A major limitation in the management of PCa is an inability to distinguish, early on, cancers that will progress and become life threatening. One‐dimensional (1D) proton (1H) MRS of the prostate provides metabolic information such as levels of choline (Ch), creatine (Cr), citrate (Cit), and spermine (Spm) that can be used to detect and diagnose PCa. Ex vivo high‐resolution magic angle spinning (HR‐MAS) of PCa specimens has revealed detection of more metabolites such as myo‐inositol (mI), glutamate (Glu), and glutamine (Gln). Due to the J‐modulation and signal overlap, it is difficult to quantitate Spm and other resonances in the prostate clearly by single‐ and multivoxel‐based 1D MR spectroscopy. This limitation can be minimized by adding at least one more spectral dimension by which resonances can be spread apart, thereby increasing the spectral dispersion. However, recording of multivoxel‐based two‐dimensional (2D) MRS such as J‐resolved spectroscopy (JPRESS) and correlated spectroscopy (L‐COSY) combined with 2D or three‐dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) using conventional phase‐encoding can be prohibitively long to be included in a clinical protocol. To reduce the long acquisition time required for spatial encoding, the echo‐planar spectroscopic imaging (EPSI) technique has been combined with correlated spectroscopy to give four‐dimensional (4D) echo‐planar correlated spectroscopic imaging (EP‐COSI) as well as J‐resolved spectroscopic imaging (EP‐JRESI) and the multi‐echo (ME) variants. Further acceleration can be achieved using non‐uniform undersampling (NUS) and reconstruction using compressed sensing (CS). Earlier versions of 2D MRS, theory of 2D MRS, spectral apodization filters, newer developments and the potential role of multidimensional MRS in PCa detection and management will be reviewed here. Copyright

Accelerating dynamic magnetic resonance imaging (MRI) for lung tumor tracking based on low-rank decomposition in the spatial-temporal domain: a feasibility study based on simulation and preliminary prospective undersampled MRI.

PURPOSE To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking. METHODS AND MATERIALS Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis of autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data. RESULTS In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details. CONCLUSIONS Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.

2D MR Spectroscopy Combined with Prior-Knowledge Fitting Is Sensitive to HCV-Associated Cerebral Metabolic Abnormalities

There is an evidence of neurocognitive dysfunction even in the absence of advanced liver disease in chronic hepatitis C virus (HCV) infection. Brain metabolism has been investigated non-invasively using one-dimensional (1D) in vivo Magnetic Resonance Spectroscopy (MRS) over three decades. Even though highly concentrated cerebral metabolites (N-acetylaspartate, creatine, choline, glutamate/glutamine, myo-inositol) have been detected using MRS, other metabolites at low concentrations (~1–3 mM or less) including glutathione, aspartate and GABA are quite difficult to observe using 1D MRS. In order to resolve overlapping resonances from a number of metabolites, a remedy is to add a second spectral dimension to the existing 1D MRS. Localized two-dimensional correlated spectroscopy (L-COSY) has been developed over the last decade to enhance the spectral dispersion by using the second spectral dimension. We have evaluated this L-COSY technique in the frontal white/gray matter regions of 14 HCV+ (mean age of 56.2 years) and 14 HCV− (mean age of 46.6 years) subjects. Our preliminary results showed significantly increased myo-inositol and glutathione in the HCV+ compared to the HCV− subjects. Hence, glutathione and myo-inositol should be considered along with other metabolites as important markers of inflammation.

Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex.

The insular cortex is injured in obstructive sleep apnea (OSA) and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective of this study was to assess whether the neural changes might result from γ‐aminobutyric acid (GABA) and glutamate alterations. We studied 14 OSA patients [mean age ± standard deviation (SD): 47.5 ± 10.5 years; nine male; apnea–hypopnea index (AHI): 29.5 ± 15.6 events h−1] and 22 healthy participants (47.5 ± 10.1 years; 11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior to mid‐regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA versus healthy subjects [GABA left: OSA n = 6: 0.36 ± 0.10 (mean ± SD), healthy n = 5: 0.62 ± 0.18; P < 0.05), right: OSA n = 11: 0.27 ± 0.09, healthy n = 14: 0.45 ± 0.16; P < 0.05; glutamate left: OSA n = 6: 1.61 ± 0.32, healthy n = 8: 0.94 ± 0.34; P < 0.05, right: OSA n = 14: 1.26 ± 0.28, healthy n = 19: 1.02 ± 0.28; P < 0.05]. GABA and glutamate levels were correlated only within the healthy group in the left insula (r: −0.9, P < 0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA.

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy

The overlap of metabolites is a major limitation in one‐dimensional (1D) spectral‐based single‐voxel MRS and multivoxel‐based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two‐dimensional (2D) J‐resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four‐dimensional (4D) echo planar J‐resolved spectroscopic imaging (EP‐JRESI). The goal of the present work was to validate two different non‐linear reconstruction methods independently using compressed sensing‐based 4D EP‐JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty‐two patients with PCa with a mean age of 63.8 years (range, 46–79 years) were investigated in this study. A 4D non‐uniformly undersampled (NUS) EP‐JRESI sequence was implemented on a Siemens 3‐T MRI scanner. The NUS data were reconstructed using two non‐linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non‐cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo‐inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP‐JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS

Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.