NIMG-21. VARIABLE RESOLUTION HYPERPOLARIZED [2-13C]PYRUVATE MRI IN HEALTHY VOLUNTEERS AND PATIENTS WITH IDH-MUTANT GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi132-vi132
Author(s):  
Sana Vaziri ◽  
Yaewon Kim ◽  
Adam Autry ◽  
Hsin-Yu Chen ◽  
Jeremy Gordon ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Signal To Noise Ratio ◽  
Tensor Decomposition ◽  
Fold Increase ◽  
Metabolic Imaging ◽  
Diffuse Glioma ◽  
Variable Resolution ◽  
Normal Appearing White Matter ◽  
Glutamate Synthesis

Abstract INTRODUCTION Mutations in isocitrate dehydrogenase (IDH) have been investigated as a prognostic biomarker in glioma. The presence of the IDH mutation (IDHm) is associated with 2-hydroxyglutarate (2HG) production and inhibition of glutamate synthesis (McBrayer, Cell 2018). Hyperpolarized carbon-13 (HP-13C) MRI enables dynamic measurements of in-vivo metabolism using a [2-13C]pyruvate labeled probe that undergoes conversion to [2-13C]lactate and [5-13C]glutamate. Here, we present HP [2-13C]pyruvate data from healthy volunteers and patients with IDHm diffuse glioma. Due to its intrinsic low signal-to-noise ratio (SNR), we demonstrate the ability of post-processing denoising to improve its utility and aid in detection of metabolic changes associated with IDHm. METHODS Dynamic HP 13C data were acquired following intravenous injection of [2-13C]pyruvate from five healthy volunteers and one patient with IDHm grade III astrocytoma. A novel multi-resolution frequency specific multislice EPI sequence was used to obtain [2-13C]pyruvate, [5-13C]glutamate, and downfield and upfield [2-13C]lactate signals (3s temporal resolution, pyruvate/lactate/glutamate spatial resolutions = 0.75x0.75cm2/ 2.25x2.25cm2/ 2.25x2.25cm2, 5 slices 3cm thick). Following phase correction, patch-based tensor decomposition denoising was applied to metabolite images. Metabolite differences between normal-appearing white matter (NAWM) and T2 lesion were examined for the patient data. RESULTS HP [2-13C]pyruvate imaging is able to simultaneously probe glycolytic ([2-13C]lactate) and oxidative ([5-13C]glutamate) metabolism. Denoised pyruvate/lactate/glutamate signals achieved a 4-9/3-6/3-7 fold increase in SNR. T2 lesion exhibited decreased glutamate-to-pyruvate and glutamate-to-lactate AUC ratios versus contralateral NAWM (p< 0.018, p < 1.5e-5), consistent with IDH mutant status. CONCLUSION We successfully demonstrated the feasibility of applying variable resolution HP [2-13C]pyruvate metabolic imaging to detect IDHm specific metabolism. This technique addresses a major hurdle in HP 13C MRI by improving SNR while permitting robust metabolism quantification. Future studies will optimize methods for acquiring and processing data to evaluate further data acquired from IDHm glioma patients. Supported by NIH T32 CA151022, P01 CA118816, and NICO.

A first-in-human phase I imaging study using hyperpolarized 1c-13 pyruvate (h-Py) in patients (pts) with localized prostate cancer (l-PCa).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4660-4660
Author(s):  
Andrea Lynne Harzstark ◽  
Vivian K. Weinberg ◽  
Krystyna Grycz ◽  
Ralph E. Hurd ◽  
Jan Henrik Ardenkjaer-Larsen ◽  
...  
Keyword(s):  
Phase I ◽  
Nuclear Polarization ◽  
Signal To Noise Ratio ◽  
Vital Signs ◽  
Imaging Study ◽  
Metabolic Imaging ◽  
Normal Prostate ◽  
Expansion Cohort ◽  
Kinetics Of

4660 Background: Preclinical studies demonstrated that the conversion of h-Py to hyperpolarized 13C lactate (h-lac) is detectable on MRI-spectroscopy and is a useful marker of differentiation in PCa. H-Py MRI provides more than 10,000-fold enhancement in signal to noise ratio (SNR), allowing for rapid detection of metabolic alterations in vivo. Hyperpolarized compounds have not been previously studied in man. Methods: Pts with biopsy-proven untreated l-PCa were enrolled in a phase I study of h-Py MRI. Following a modified 3+3 design, 6 pts were enrolled at each dose level (0.14, 0.28 and 0.43 mL/Kg): 3 to monitor kinetics of h-Py, and 3 to evaluate the spatial distribution of metabolism in PCa and normal prostate (nl-P). An expansion cohort of 15 pts explored the biological variability of metabolism. A dynamic nuclear polarization (DNP) system, the first human system anywhere, generated and delivered 230 mM sterile h-Py. IV injection of h-Py was followed by imaging with a 3T MR scanner with custom transmit and receive coils. Monitoring included EKG, vital signs, and laboratory testing. Results: 31 pts were imaged. 23 pts had Gleason (G) 6, 6 pts G7, and 2 pts G8 PCa. Median age was 63 years (range 45-75); median PSA was 5.9 ng/mL (1.88-20.2). No dose limiting toxicities or >grade (gr) 2 toxicity was observed. Toxicity included: gr 1dysgeusia (6 pts), gr 1 hypokalemia, gr 1 hypocalcemia, gr 1 dizziness, and gr 2 diarrhea (1 pt each). Median time from dissolution of the agent to delivery into patients was 66 seconds (43-88). Signals from h-Py and h-Lac were seen in PCa and nl-P at all doses; 0.43 mL/Kg showed the best SNR and discrimination between PCa and nl-P and was therefore established as the phase II dose. There appeared to be an association between h-Lac levels and PCa grade. Conclusions: H-py metabolic imaging has minimal toxicity and provides the ability to discriminate Ca from nl-P based on increased levels of h-lac. The correlation with grade and changes with therapy require further study.

scholarly journals Removing independent noise in systems neuroscience data using DeepInterpolation

2020 ◽  
Author(s):  
Jérôme Lecoq ◽  
Michael Oliver ◽  
Joshua H. Siegle ◽  
Natalia Orlova ◽  
Christof Koch
Keyword(s):  
Temporal Resolution ◽  
Signal To Noise Ratio ◽  
Scientific Discovery ◽  
Fold Increase ◽  
General Purpose ◽  
Scientific Discipline ◽  
Missed Opportunities ◽  
Standard Data ◽  
Spatio Temporal

Progress in nearly every scientific discipline is hindered by the presence of independent noise in spatiotemporally structured datasets. Three widespread technologies for measuring neural activity—calcium imaging, extracellular electrophysiology, and fMRI—all operate in domains in which shot noise and/or thermal noise deteriorate the quality of measured physiological signals. Current denoising approaches sacrifice spatial and/or temporal resolution to increase the Signal-to-Noise Ratio of weak neuronal events, leading to missed opportunities for scientific discovery.Here, we introduce DeepInterpolation, a general-purpose denoising algorithm that trains a spatio-temporal nonlinear interpolation model using only noisy samples from the original raw data. Applying DeepInterpolation to in vivo two-photon Ca2+ imaging yields up to 6 times more segmented neuronal segments with a 15 fold increase in single pixel SNR, uncovering network dynamics at the single-trial level. In extracellular electrophysiology recordings, DeepInterpolation recovered 25% more high-quality spiking units compared to a standard data analysis pipeline. On fMRI datasets, DeepInterpolation increased the SNR of individual voxels 1.6-fold. All these improvements were attained without sacrificing spatial or temporal resolution.DeepInterpolation could well have a similar impact in other domains for which independent noise is present in experimental data.

scholarly journals PET by MRI: Glucose Imaging by 13C-MRS without Dynamic Nuclear Polarization by Noise Suppression through Tensor Decomposition Rank Reduction

2018 ◽  
Author(s):  
Jeffrey R. Brender ◽  
Shun Kishimoto ◽  
Hellmut Merkle ◽  
Galen Reed ◽  
Ralph E. Hurd ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Fdg Pet ◽  
Noise Suppression ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Tensor Decomposition ◽  
Fold Increase ◽  
Metabolic Reprogramming ◽  
Resonance Spectroscopy

AbstractMetabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only. 13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements. We show here a new method of imaging glucose metabolism in vivo that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12 s and an overall spatial resolution that compares favorably to 18F-FDG PET.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Effects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers

2019 ◽  
Vol 130 ◽  
pp. 32-43 ◽  
Author(s):  
Elias Begas ◽  
Maria Bounitsi ◽  
Thomas Kilindris ◽  
Evangelos Kouvaras ◽  
Konstantinos Makaritsis ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Crocus Sativus ◽  
Short Term ◽  
Metabolizing Enzymes ◽  
Xenobiotic Metabolizing Enzymes ◽  
Crocus Sativus L

scholarly journals Quantitative Swept-Source Optical Coherence Tomography of Early Enamel Erosion in vivo

2017 ◽  
Vol 51 (4) ◽  
pp. 410-418 ◽  
Author(s):  
Rupert S. Austin ◽  
Maisalamah Haji Taha ◽  
Frederic Festy ◽  
Richard Cook ◽  
Manoharan Andiappan ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Healthy Volunteers ◽  
Orange Juice ◽  
Signal Intensity ◽  
Surface States ◽  
Enamel Surface ◽  
Optical Coherence ◽  
Swept Source ◽  
Water Rinsing

Swept-source optical coherence tomography (SS-OCT) shows potential for the in vivo quantitative evaluation of micro-structural enamel surface phenomena occurring during early erosive demineralization. This randomized controlled single-blind cross-over clinical study aimed to evaluate the use of SS-OCT for detecting optical changes in the enamel of 30 healthy volunteers subjected to orange juice rinsing (erosive challenge) in comparison to mineral water rinsing (control), according to wiped and non-wiped enamel surface states. Participants were randomly allocated to 60 min of orange juice rinsing (pH 3.8) followed by 60 min of water rinsing (pH 6.7) and vice versa, with a 2-week wash-out period. In addition, the labial surfaces of the right or left maxillary incisors were wiped prior to SS-OCT imaging. An automated ImageJ algorithm was designed to analyse the back-scattered OCT signal intensity (D) after orange juice rinsing compared to after water rinsing. D was quantified as the OCT signal scattering from the 33 µm sub-surface enamel, normalised by the total OCT signal intensity entering the enamel. The back-scattered OCT signal intensity increased by 3.1% (95% CI 1.1-5.1%) in the wiped incisors and by 3.5% (95% CI 1.5-5.5%) in the unwiped incisors (p < 0.0001). Wiping reduced the back-scattered OCT signal intensity by 1.7% (95% CI -3.2 to -0.3%; p = 0.02) in comparison to the unwiped enamel surfaces for both rinsing solutions (p = 0.2). SS-OCT detected OCT signal changes in the superficial sub-surface enamel of maxillary central incisor teeth of healthy volunteers after orange juice rinsing.

scholarly journals Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 504
Author(s):  
Seunggwi Park ◽  
Hashizume Rintaro ◽  
Seul Kee Kim ◽  
Ilwoo Park
Keyword(s):  
Metabolic Imaging ◽  
Metabolic Profiles ◽  
Rodent Models ◽  
In Vivo Metabolism ◽  
Hyperpolarized 13C ◽  
Noninvasive Assessment ◽  
Diffuse Midline Glioma ◽  
Mr Spectroscopic Imaging

The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.

scholarly journals Ultra-high-field 7-T MRI in multiple sclerosis and other demyelinating diseases: from pathology to clinical practice

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolo’ Bruschi ◽  
Giacomo Boffa ◽  
Matilde Inglese
Keyword(s):  
Multiple Sclerosis ◽  
High Field ◽  
Neurological Diseases ◽  
Lesion Detection ◽  
Demyelinating Diseases ◽  
Metabolic Imaging ◽  
Central Vein ◽  
Ultra High Field ◽  
Functional Features

Abstract Magnetic resonance imaging (MRI) is essential for the early diagnosis of multiple sclerosis (MS), for investigating the disease pathophysiology, and for discriminating MS from other neurological diseases. Ultra-high-field strength (7-T) MRI provides a new tool for studying MS and other demyelinating diseases both in research and in clinical settings. We present an overview of 7-T MRI application in MS focusing on increased sensitivity and specificity for lesion detection and characterisation in the brain and spinal cord, central vein sign identification, and leptomeningeal enhancement detection. We also discuss the role of 7-T MRI in improving our understanding of MS pathophysiology with the aid of metabolic imaging. In addition, we present 7-T MRI applications in other demyelinating diseases. 7-T MRI allows better detection of the anatomical, pathological, and functional features of MS, thus improving our understanding of MS pathology in vivo. 7-T MRI also represents a potential tool for earlier and more accurate diagnosis.

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