Quantitative T1-relaxation corrected metabolite mapping of 12 metabolites in the human brain at 9.4 T

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging modality that enables observation of metabolites. Applications of MRSI for neuroimaging applications has shown promise for monitoring and detecting various diseases. This study builds off previously developed techniques of short TR, 1H FID MRSI by correcting for T1-weighting of the metabolites and utilizing an internal water reference to produce quantitative (mmol kg-1) metabolite maps. This work reports and shows quantitative metabolite maps for 12 metabolites for a single slice. Voxel-specific T1-corrections for water are common in MRSI studies; however, most studies use either averaged T1-relaxation times to correct for T1-weighting of metabolites or omit this correction step entirely. This work employs the use of voxel-specific T1-corrections for metabolites in addition to water. Utilizing averaged T1-relaxation times for metabolites can bias metabolite maps for metabolites that have strong differences between T1-relaxation for GM and WM (i.e. Glu). This work systematically compares quantitative metabolite maps to single voxel quantitative results and qualitatively compares metabolite maps to previous works.

Genetic and Mitochondrial Metabolic Analyses of an Atypical Form of Leigh Syndrome

In this study, we aimed to establish the mitochondrial etiology of the proband’s progressive neurodegenerative disease suggestive of an atypical Leigh syndrome, by determining the proband’s pathogenic variants. Brain MRI showed a constellation of multifocal temporally disparate lesions in the cerebral deep gray nuclei, brainstem, cerebellum, spinal cord along with rhombencephalic atrophy, and optic nerve atrophy. Single voxel 1H MRS performed concurrently over the left cerebral deep gray nuclei showed a small lactate peak, increased glutamate and citrate elevation, elevating suspicion of a mitochondrial etiology. Whole exome sequencing revealed three heterozygous nuclear variants mapping in three distinct genes known to cause Leigh syndrome. Our mitochondrial bioenergetic investigations revealed an impaired mitochondrial energy metabolism. The proband’s overall ATP deficit is further intensified by an ineffective metabolic reprogramming between oxidative phosphorylation and glycolysis. The deficient metabolic adaptability and global energy deficit correlate with the proband’s neurological symptoms congruent with an atypical Leigh syndrome. In conclusion, our study provides much needed insights to support the development of molecular diagnostic and therapeutic strategies for atypical Leigh syndrome.

Multi-echo Dixon and breath-hold T2-corrected multi-echo single-voxel MRS for quantifying hepatic iron overload in rabbits

Background Three-dimensional (3D) multi-echo-Dixon (ME-Dixon) and breath-hold T2-corrected multi-echo single-voxel MR spectroscopy (HISTO) can simultaneously quantify liver fat and liver iron. However, their diagnostic efficacy and application scope for quantitative iron in co-existing fatty liver have not been adequately evaluated. Purpose To evaluate the accuracy of ME-Dixon and HISTO for quantitative analysis of hepatic iron in rabbits with iron deposition and fatty liver using liver–iron concentration (LIC) as a reference standard. Material and Methods ME-Dixon, HISTO, and conventional two-dimensional multi-echo gradient echo (GRE) sequences were performed on 42 rabbits. The following parameters were calculated: R2* from ME-Dixon and GRE; proton density fat fraction (PDFF) from the ME-Dixon, HISTO (normal TE range), and HISTO-H (extended TE range); and R2_water from HISTO and HISTO-H. The LIC and liver–fat concentration (LFC) were measured through chemical analysis, and their relationship with the MRI parameters were assessed. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic efficiency. Results LIC was significantly correlated with R2_HISTO-H, R2*_Dixon, and R2*_GRE ( r = 0.858, 0.910, 0.931, respectively; P < 0.001) and weakly with R2_HISTO ( r = 0.424; P = 0.008). A strong correlation was also observed between the LFC and PDFF obtained from HISTO, HISTO-H, and ME-Dixon ( r = 0.776, 0.811, 0.888, respectively; P < 0.001). ME-Dixon showed the best performance with moderate iron overload (AUC = 0.983). Conclusion 3D ME-Dixon is useful for quantifying the LIC, especially with co-existing fatty liver. Its diagnostic performance is also superior to that of the HISTO sequence.

NIfTI-MRS: A standard format for magnetic resonance spectroscopic data

Purpose: The use of multiple data formats in the MRS community currently hinders data sharing and integration. NIfTI-MRS is proposed as a standard MR spectroscopy data format, which is implemented as an extension to the neuroimaging informatics technology initiative (NIfTI) format. Using this standardised format will facilitate data sharing, ease algorithm development, and encourage the integration of MRS analysis with other imaging modalities. Methods: A file format based on the NIfTI header extension framework was designed to incorporate essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open-source command-line conversion program is implemented to enable conversion of single-voxel and spectroscopic imaging data to NIfTI-MRS. To provide visualisation of data in NIfTI-MRS, a dedicated plugin is implemented for FSLeyes, the FSL image viewer. Results: Alongside online documentation, ten example datasets are provided in the proposed format. In addition, minimal examples of NIfTI-MRS readers have been implemented. The conversion software, spec2nii, currently converts fourteen formats to NIfTI-MRS, including DICOM and vendor proprietary formats. Conclusion: The proposed format aims to solve the issue of multiple data formats being used in the MRS community. By providing a single conversion point, it aims to simplify the processing and analysis of MRS data, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. It also opens possibility of greater standardisation and harmonisation. By aligning with the dominant format in neuroimaging, NIfTI-MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, as a viewer.

NIMG-15. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN ADULT BRAINSTEM GLIOMA PATIENTS

OBJECTIVE The onco-metabolite, 2-Hydroxyglutarate (2HG), is non-invasive biomarker for detecting isocitrate dehydrogenase (IDH) mutant glioma by MR-Spectroscopy. Especially 2HG-MRS may be useful in patients with brainstem lesions, where surgical biopsy presents high risk of neurological injury. Here, we examined the utility of 2HG-MRS for diagnosis of IDH mutant adult brainstem glioma. METHODS We conducted 3 tesla -MRS (3T-MRS) in 8 radiographically identified brainstem tumor (7 male and 1 female, median age 39). Single-voxel was localized from the T2-FLAIR using a 2HG-tailored MRS protocol (Philips, Achieva, PRESS, TE 35 ms). All patients underwent tumor biopsy using an intraoperative navigation system (Brain LABTM) or stereotactic biopsy system (Komai’s CT-stereotactic frame) before initial treatment. IDH and H3K27M status were diagnosed by IHC and DNA sequence. RESULTS 3 cases were H3K27M and 4 cases were IDH mutant (R132H 1 case, R132S 2 cases, and R132G 1 case). 1 case were neither H3K27M nor IDH mutant. H3-K27 and IDH1 mutations were mutually exclusive. All tumor located at pons. There were no significant radiological difference between H3K27M and IDH mutant in conventional MRI sequence. Pearson's chi-square test demonstrated that 2HG concentrations &gt;1.5 mM were 100% sensitive and 75% specific for IDH mutant glioma (p = 0.0285). The median overall survival survival were 127 month in IDH mutant glioma (n=4) and 22.5 months in IDH wild-type glioma (n=4), respectively. CONCLUSIONS 2HG in adult brainstem glioma was detected by conventional 3T-MRS successfully. A noninvasive 2HG-MRS may be useful diagnostic modality for evaluating molecular status and prognosis in brainstem glioma noninvasively.

MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review

Neuroimaging has been a critical tool for understanding the neuropathological underpinnings observed in HIV. The pathophysiology of HAND is chiefly driven by neuroinflammation. Despite adhering to cART, low levels of viraemia probably persist in the brain in some patients leading to chronic immune activation with resultant neuroinflammation and consequent neuronal injury. MR spectroscopy has been widely used as a biomarker for the presence and severity of HAND in several studies. By studying the MRS signatures, it is possible to characterise the presence of neuroinflammation and neural injury. Furthermore, metabolite concentrations measured by MRS could be used as a quantitative indicator of HIV cerebral involvement, thereby affording the opportunity to assess the efficacy of cART in HAND. However, currently there are three significant limitations in the MRS HIV research literature: the relative paucity of prospective studies, the small number of regions of interrogation due to current methodology (single voxel MRS), and the evolving understanding of the impact of co-morbidities (e.g. ageing, mood disorders, alcoholism etc.) on MRS measurements. This review critically addresses the current literature of MRS studies in people living with HIV (PWH) with HAND to determine its value, especially in the context of the current cART era. In addition, we discuss technical considerations related to the disease and the future direction in HAND using MRS.

Identification of potential metabolic biomarkers in predicting esophageal varices needing treatment in patients with liver cirrhosis

The goal of this study was to determine the diagnostic performance of in vivo quantitative proton magnetic resonance spectroscopy (1H-MRS) to identify the presence of esophageal varices needing treatment (VNT), as well as investigate its correlation with clinical characteristics in patients with liver cirrhosis. Forty cirrhotic patients without VNT showing the negative red color sign, and 40 cirrhotic patients with VNT showing positive red color sign underwent laboratory tests, esophago-gastro-duodenoscopy, and 1H-MRS with single-voxel localization in the cirrhotic liver parenchyma. The levels of lactate + triglyceride (TG) and choline in cirrhotic patients with VNT were significantly higher than those in cirrhotic patients without VNT. In multivariate analysis, spleen diameter, platelet count, and platelet count/spleen diameter ratio, as well as lactate + TG, and choline were associated with the presence of VNT. Moreover, lactate + TG and choline levels were positively correlated with spleen diameter and negatively correlated with platelet count in the combined group of cirrhotic patients with and without VNT. Our study demonstrated that higher hepatic lactate + TG and choline levels in cirrhotic patients in conjunction with longer spleen diameter, lower platelet counts, and lower ratios of platelet count to spleen diameter were associated with the presence of esophageal VNT and the risk of developing variceal bleeding. Therefore, in vivo 1H-MRS might be an effective tool for diagnosing and predicting esophageal VNT in patients with liver cirrhosis.