New Horizons in Hyperpolarized 13C MRI

Hyperpolarized (HP) 13C MRI has shown promise as a valuable modality for in vivo measurements of metabolism and is currently in human trials at 15 research sites worldwide. With this growth, it is important to adopt standardized data storage practices as it will allow sites to meaningfully compare data. In this paper, we (1) describe data that we believe should be stored and (2) demonstrate pipelines and methods that utilize the Digital Imaging and Communications in Medicine (DICOM) standard. This includes proposing a set of minimum set of information that is specific to HP 13C MRI studies. We then show where the majority of these can be fit into existing DICOM attributes, primarily via the "Contrast/Bolus" module. We also demonstrate pipelines for utilizing DICOM for HP 13C MRI. DICOM is the most common standard for clinical medical image storage and provides the flexibility to accommodate the unique aspects of HP 13C MRI, including the HP agent information but also spectroscopic and metabolite dimensions. The pipelines shown include creating DICOM objects for studies on human and animal imaging systems with various pulse sequences. We also show a python-based method to efficiently modify DICOM objects to incorporate the unique HP 13C MRI information that is not captured by existing pipelines. Moreover, we propose best practices for HP 13C MRI data storage that will support future multi-site trials, research studies, and technical developments of this imaging technique.

Recently, both Magnetic Resonance (MR) Imaging (MRI) and Spectroscopy (MRS) have emerged as promising tools for detection of prostate cancer (CaP). However, due to the inherent dimensionality differences in MR imaging and spectral information, quantitative integration of T(2) weighted MRI (T(2)w MRI) and MRS for improved CaP detection has been a major challenge. In this paper, we present a novel computerized decision support system called multimodal wavelet embedding representation for data combination (MaWERiC) that employs, (i) wavelet theory to extract 171 Haar wavelet features from MRS and 54 Gabor features from T(2)w MRI, (ii) dimensionality reduction to individually project wavelet features from MRS and T(2)w MRI into a common reduced Eigen vector space, and (iii), a random forest classifier for automated prostate cancer detection on a per voxel basis from combined 1.5 T in vivo MRI and MRS. A total of 36 1.5 T endorectal in vivo T(2)w MRI and MRS patient studies were evaluated per voxel by MaWERiC using a three-fold cross validation approach over 25 iterations. Ground truth for evaluation of results was obtained by an expert radiologist annotations of prostate cancer on a per voxel basis who compared each MRI section with corresponding ex vivo wholemount histology sections with the disease extent mapped out on histology. Results suggest that MaWERiC based MRS T(2)w meta-classifier (mean AUC, μ = 0.89 ± 0.02) significantly outperformed (i) a T(2)w MRI (using wavelet texture features) classifier (μ = 0.55 ± 0.02), (ii) a MRS (using metabolite ratios) classifier (μ = 0.77 ± 0.03), (iii) a decision fusion classifier obtained by combining individual T(2)w MRI and MRS classifier outputs (μ = 0.85 ± 0.03), and (iv) a data combination method involving a combination of metabolic MRS and MR signal intensity features (μ = 0.66 ± 0.02).

Magnetic resonance imaging and spectroscopy (MRI/MRS) at 7T represents an exciting advance in MR technology, with intriguing possibilities to enhance image spatial, spectral, and contrast resolution. To ensure the safe use of this technology while still harnessing its potential, clinical staff and researchers need to be cognizant of some safety concerns arising from the increased magnetic field strength and higher Larmor frequency. The higher static magnetic fields give rise to enhanced transient bioeffects and an increased risk of adverse incidents related to electrically conductive implants. Many technical challenges remain and the continuing rapid pace of development of 7T MRI/MRS is likely to present further challenges to ensuring safety of this technology in the years ahead. The recent regulatory clearance for clinical diagnostic imaging at 7T will likely increase the installed base of 7T systems, particularly in hospital environments with little prior ultrahigh-field MR experience. Informed risk/benefit analyses will be required, particularly where implant manufacturer-published 7T safety guidelines for implants are unavailable. On behalf of the International Society for Magnetic Resonance in Medicine, the aim of this article is to provide a reference document to assist institutions developing local institutional policies and procedures that are specific to the safe operation of 7T MRI/MRS. Details of current 7T technology and the physics underpinning its functionality are reviewed, with the aim of supporting efforts to expand the use of 7T MRI/MRS in both research and clinical environments. Current gaps in knowledge are also identified, where additional research and development are required. Level of Evidence 5 Technical Efficacy 2 J. MAGN. RESON. IMAGING 2021;53:333-346.

Advances in quantitative magnetic resonance imaging and spectroscopy (MRI/MRS) methodology have enabled probing tissue microstructure and function with exquisite specificity and sensitivity in human and model systems. Using this technology to examine changes in tissue microstructure and function in aging or pathology has the potential to provide a window into the underlying age-related diseases’ mechanisms, and to nominate MR biomarkers for longitudinal assessment and intervention. Water molecules within biological tissues undergo interactions with their environment through nuclear relaxation, magnetization transfer, chemical exchange, and diffusion. These processes are sensitive to underlying local tissue properties such as density, microstructure, temperature, acidity, composition, and geometry. Through use of combinations of magnetic fields and radiofrequency pulse formalisms, MRI/MRS provides unique sensitivity and specificity to probe these mechanisms in all biological tissues. Advances in acquisition strategies, hardware designs, computational analyses, and signal modeling have positioned MRI/MRS as powerful emerging noninvasive modalities to studying biological tissue to differentiate normal from abnormal cell-level processes. These techniques are based on multicomponent relaxometry or diffusion, magnetization transfer, high-dimensional imaging or spectroscopy, susceptibility imaging, cerebral functioning, etc. However, their integration in clinical trials and investigations is still limited. This session will provide an overview about these emerging MRI/MRS techniques, their value and application in studying aging. The overarching goal is to generate further interest within the scientific community, disseminate and integrate these mature and unique noninvasive approaches in research settings and routine clinical protocols to advance our understanding of aging processes.

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the “HP 13C MRI Consensus Group” as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality.

Nuclear magnetic resonance spectroscopy and imaging (MRI) play an indispensable role in science and healthcare but use only a tiny fraction of their potential. No more than ≈10 p.p.m. of all 1H nuclei are effectively detected in a 3-Tesla clinical MRI system. Thus, a vast array of new applications lays dormant, awaiting improved sensitivity. Here we demonstrate the continuous polarization of small molecules in solution to a level that cannot be achieved in a viable magnet. The magnetization does not decay and is effectively reinitialized within seconds after being measured. This effect depends on the long-lived, entangled spin-order of parahydrogen and an exchange reaction in a low magnetic field of 10−3 Tesla. We demonstrate the potential of this method by fast MRI and envision the catalysis of new applications such as cancer screening or indeed low-field MRI for routine use and remote application.

Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used to follow the time course of ethanol-induced fatty liver in a group of 10 rats fed a diet containing 12% alcohol (ethanol) over a 5-week period. The MR data consisted of T1-weighted images, in vivo 1H spectra, and in vivo T1 relaxation measurements. Changes in short TR images as a result of fatty accumulation were noted only as a slight increase in liver intensity relative to surrounding muscle. A poorly correlated (r = 0.54) increase in water T1 with time was observed. No statistically significant changes in lipid T1 were found. MRS derived lipid content was compared with biochemically derived total lipids and histology. MRS determined liver lipids were found to increase linearly with time (r = 0.91). Biochemically derived lipid content also increased with prolonged exposure to ethanol (r = 0.96). The averages of MRS derived lipid content agreed well with the average changes in biochemically determined total lipid concentration. Histologic examination revealed slight to moderate changes in fatty accumulation with significant variation in the group at the end of the study. On an individual basis the MRS and histologic evaluation were highly correlated (r = 0.94).

To explore the usefulness of magnetic resonance imaging (MRI) and spectroscopy (MRS) for assessment of non-alcoholic fat liver disease (NAFLD) as compared with liver histological and metabolomics findings. Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesity-induced NAFLD in an observational, prospective, single-site, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described (1)H NMR-based metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from (1)H NMR spectra obtained after surgery were omitted due to technical limitations. MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, which excluded the presence of non-alcoholic steatohepatitis (NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the -CH3 peak (0.9 ppm), the -CH2- peak (1.3 ppm, mostly triglyceride) and the -CH=CH- peak (2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may help to explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients. MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose.

Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism

The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). Peak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675 +/- 84 cm3/m2; HF, 567 +/- 112 cm3/m2; p less than 0.05). Fat stores were largely preserved with triceps skinfold of less than 5% of normal and/or IBW of less than 80% in only 8% of patients. Modest linear correlations were observed between peak VO2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p less than 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = -0.42, p less than 0.05). These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.

The advent of magnetic resonance imaging (MRI) and spectroscopy (MRS) and of single photon and positron emission tomography (SPET:PET) has allowed acquisition of data, not otherwise available, on cerebral metabolic function in patients with hepatic encephalopathy. Hyperintensity of the globus pallidus has been observed in cerebral T1-weighted MR images in patients with sub-clinical or overt hepatic encephalopathy, most likely due to the deposition of manganese; these trace metal deposits reflect either intoxication or the presence of an adaptive process leading to improved efficacy of ammonia detoxification by astrocytes. Cerebral 31P MRS has shown that there is no primary deficit in energy metabolism in patients with hepatic encephalopathy, but rather an impairment of phospholipid membrane metabolism; cerebral 1H MRS shows a characteristic pattern of abnormalities in these patients, namely, a significant increase in glutamine/glutamate and significant reductions in choline-containing compounds associated with phospholipid membrane metabolism and of myo-inositol which functions, in part, as an organic osmolyte. SPET and PET technology have not been adequately exploited in the study of hepatic encephalopathy to date; the few studies available have produced conflicting results, most likely because little or no account was taken of the effects of chronic liver disease, portal-systemic shunting or enhanced blood-brain barrier permeability on tracer-ligand availability. All of these techniques need to be further exploited in well-characterized populations with, wherever possible, standardization of techniques between centers; the factors likely to affect tracer-ligand availability must be adequately controlled to allow correct interpretation of the data obtained.

Multi‐channel phased receive arrays have been widely adopted for magnetic resonance imaging (MRI) and spectroscopy (MRS). An important step in the use of receive arrays for MRS is the combination of spectra collected from individual coil channels. The goal of this work was to implement an improved strategy termed OpTIMUS (i.e., optimized truncation to integrate multi‐channel MRS data using rank‐Rsingular value decomposition) for combining data from individual channels. OpTIMUS relies on spectral windowing coupled with a rank‐R decomposition to calculate the optimal coil channel weights. MRS data acquired from a brain spectroscopy phantom and 11 healthy volunteers were first processed using a whitening transformation to remove correlated noise. Whitened spectra were then iteratively windowed or truncated, followed by a rank‐R singular value decomposition (SVD) to empirically determine the coil channel weights. Spectra combined using the vendor‐supplied method, signal/noise2 weighting, previously reported whitened SVD (rank‐1), and OpTIMUS were evaluated using the signal‐to‐noise ratio (SNR). Significant increases in SNR ranging from 6% to 33% (P ≤ 0.05) were observed for brain MRS data combined with OpTIMUS compared with the three other combination algorithms. The assumption that a rank‐1 SVD maximizes SNR was tested empirically, and a higher rank‐R decomposition, combined with spectral windowing prior to SVD, resulted in increased SNR.

The in vivo study of molecular processes in human bone marrow is important for both diagnostics and understanding of disease pathophysiology. Traditionally, the hematopoietic component of the bone marrow has been a research focus, but recently, the role of bone marrow adipose tissue has been gaining interest in many applications. The purpose of the present review is to give an overview of existing imaging modalities allowing in vivo molecular imaging of bone marrow adipose tissue in humans with an emphasis on technical aspects: the characteristics of the extracted parameters and their application in bone marrow adipose tissue. Magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) are the most frequently used imaging methods for the examination of bone marrow adipose tissue as they provide rich soft tissue contrast and come without ionizing radiation. Existing MR methods allow the extraction of many different measures including proton density fat fraction, fatty acid characteristics, and diffusion and perfusion properties. However, many available techniques have to be carefully adjusted to be used in the investigation of the fat signal component, especially in the presence of trabecular bone. Dual-energy computed tomography (DECT) is an emerging technique—not yet widely available—which appears to be a promising alternative to MR for rapid fat fraction assessment. Positron emission tomography (PET) allows additional functional metabolic imaging and therefore provides valuable additional information (e.g., glucose uptake) to MR-based parameters at the cost of ionizing radiation. Bone marrow imaging still appears to be a niche with remaining technical challenges using existing imaging modalities. A good working knowledge of the underlying physical and technical principles is required as most techniques are yet not available out of the box and may need to be adjusted to fit the requirements for bone marrow adipose tissue imaging. In summary, MR, DECT, and PET enable the measurement of several inherently different parameters in in vivo molecular imaging of bone marrow adipose tissue. The growing interest for molecular imaging markers of bone marrow, thanks to its high metabolic and clinical significance, may eventually lead to new developments, as well as improvements of emerging techniques as soon as they become more broadly available.

To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity. Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS). Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatric manifestations, or end-organ involvement compared to patients without migraine (p > 0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache (p > 0.05). Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.

Motivation: Recent studies suggest that HCM may be fundamentally a metabolic disease. Goal(s): We sought to explore any correlations between metabolism and late gadolinium enhancement in the myocardium that may provide further information on the various metabolic phenotypes of HCM. Approach: We used hyperpolarized 13C-pyruvate MRI to quantify myocardial glycolytic and TCA metabolism and compared this to late gadolinium enhancement (LGE%) from clinical CMR. Results: The findings support the hypothesis that HCM has a significant metabolic component and suggest that HP 13C-MRI could become a valuable tool for characterizing metabolic phenotypes in HCM, potentially aiding in diagnosis, prognosis, and treatment monitoring. Impact: Standard-of-care cardiac magnetic resonance (CMR) provides information on physical form and function, but it does not offer metabolic information on tissue and such information from hyperpolarized 13C MRI could aid in diagnosis and translation of metabolic therapies.