HIGHER SPEED, FIELD AND SPATIAL RESOLUTION BRAIN 3D 1H MRS
Gonen Oded, Professor Or Radiology And Neu
New York University School Of Medicinecity: New York country: United States (us)
Grant 5R01EB001015-16 from National Institute Of Biomedical Imaging And Bioengineering
Abstract: Metabolic changes observed with proton-magnetic-resonance-spectroscopy (1H-MRS) often augment the highly sensitive but not specific MRI. Indeed, at 1.5 Tesla, 1H-MRS has so far linked anatomy from MRI with underlying metabolism in cancer, Alzheimer´s and Parkinson´s diseases, MS, HIV, epilepsy, stroke trauma and other neurological and psychiatric disorders. It was anticipated, therefore, that high, B0 e3 T, magnetic-fields would provide 1H-MRS a much needed boost in sensitivity, spectral and spatial resolution. That unfortunately, did not happen despite their proliferation in number, 300 installed, and field strength, up to 9.4 T. Translation of the most useful two and three dimensional (2D, 3D) 1H-MRS techniques to high-fields has been stymied by (i) High radio-frequency (B1) power requirements and heat deposition; (ii) short T2s, reducing the signal-to- noise-ratio (SNR) gain; (iii) chemical shift displacement errors; and (iv) lack of software to evaluate and display the large data sets. Consequently, efficient, reliable 3D multivoxel techniques are not offered by instrument manufacturers, who traditionally shift this onus onto publicly-funded academic research. The long term goal of this competing continuation, therefore, is to develop methods to address issues i - iv to perform 3D 1H-MRS at higher B0s, and realize the advantages for clinical research. Our response to these problems is to extend to 3 and 7 T our successful hybrid techniques. Specific Aim 1 is to exploit the shorter T2s to enhance the SNR and acquisition efficiency of 3D coverage by optimal interleaving across the volume-of-interest (VOI), multiple slabs of several slices each. Specific Aim 2 is to overcome the declining B1 fields per watt RF power with shifted-Hadamard pulses that need the B1 of just one slice to sequentially excite several. This will lower the peak and deposited power under very strong selective gradients and reduce the chemical shift displacement. Specific Aim 3, is to recover the SNR lost to shorter T2s at high B0s with non-echo sequences using 3D transverse and longitudinal-Hadamard encoding to define the VOI. Finally, Specific Aim 4 is to develop new post-processing methods to detect and visualize relationships between different metabolites´ spatial distributions to simplify the daunting amounts of 3D 1H MRS data. This project will lead to increases in the amount of human brain volume covered in an exam, improve the localization accuracy as well as spatial and spectral resolution and shorten the acquisition time for proton spectroscopy at higher magnetic fields. These capabilities will enhance studies of the underlying metabolism of devastating (but frequently MRI-invisible or of non-specific finding) neurological diseases in the human brain and spine and may also improve our capability to monitor the effectiveness of their treatment(s)
Keywords: Address; Algorithms; Alzheimer`s Disease; Anatomy; base; Brain; brain volume; CD80 gene; Cervical spine; Characteristics; Chemical Shift Imaging; Chemicals; Clinical Research; Coiled Bodies; Color; Computer software; Coupled; cranium; Data; Data Set; Deposition; Detection; Development; Disease; Effectiveness; Epilepsy; falls; Frequencies (time pattern); Funding; Goals; Heating; HIV; Human; human subject; Hybrids; Image; image processing; Imagery; improved; in vivo; instrument; interest; Lead; Link; Lipids; magnetic field; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Manufacturer Name; Maps; Mental disorders; Metabolic; Metabolism; Methods; Monitor; Morphologic artifacts; nervous system disorder; Neuraxis; Noise; novel; Parkinson Disease; Pattern; Performance; Physiologic pulse; Predisposition; Process; Proliferating; Protons; Radio; Recycling; Relaxation; Research; research study; Resolution; response; Scheme; Signal Transduction; Slice; Spatial Distribution; Spectrum Analysis; Speed (motion); stroke; Sum; Surface; Techniques; Technology; Testing; Thick; Time; Tissues; tool; Translating; Translations; Trauma; Uncertainty; Vertebral column; volunteer
Project start date: 1996-07-22
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-07-070
5R01EB001015-16 (2011): $634210
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Gonen Oded
SERIAL BRAIN 3D 1H MR SPECTROSCOPY IN MULTIPLE SCLEROSIS
Gonen Oded, Professor Or Radiology And Neu
New York University School Of Medicinecity: New York country: United States (us)
Grant 5R01NS050520-05 from National Institute Of Neurological Disorders And Stroke
Abstract: Clinical T2 and contrast-enhanced Tl-weighted magnetic resonance imaging (MRI) have become the diagnostic modalities of choice in the evaluation of multiple sclerosis (MS) due to their sensitivity to acute, often subclinical events in the brain and their ability to measure the accumulation of the disease over time. MRI, however, lacks specificity, in that to date, there are conflicting reports concerning the number and volume of these lesions, "the load of the disease," and the associated neurological deficits. Furthermore, clinical MRI is completely blind to occult white matter (WM) and most gray matter (GM) pathology. The need for more reliable surrogate markers frequently leads to proton magnetic resonance spectroscopy 1HMRS being used to probe the underlying metabolism of normal appearing WM (NAWM) and the lesions in it. Since MS pathogenesis starts on molecular cellular levels, we propose to use state of the art, short echotime, three-dimensional high-spatial resolution local and global 1H-MRS methods to examine three hypotheses HI That MS lesions develop in WM regions which are already metabolically abnormal; H2 Abnormal metabolic activity persists in NAWM and lesions even absent Gd-enhancement (the current marker of "activity"); and H3 That global whole-brain quantification of the decline rate of the neuronal cell marker N-acetylaspartate (NAA) reflects the aggressiveness of a patient´s disease, and therefore, could forecast its future course in that individual. These hypotheses will be tested by following a cohort of 25 relapsingremitting (RR) MS patients and 25 matched controls, for 5 years, with three Specific Aims Specific Aim 1 is to perform longitudinal follow-up of the overall metabolites levels in the NAWM to establish markers for current MRI-occult disease activity. Specific Aim 2 is to follow localized metabolism in NAWM to determine what focal changes preceded lesion formation and determine those lesions´ outcome - to repair or become chronic. Specific Aim 3 is to correlate the NAA levels of the whole brain and its WM and GM fractions with the patients´ clinical deficits to establish the NAA as a forecaster of disease severity and future course. The health relatedness of this study is its potential to establish, quantify and validate non-invasive radiological metabolic surrogate markers of RR MS progression that will enable us to (i) Gauge current level of disease activity, thereby, (ii) increase our capability to forecast its future course for these (young) patients; and consequently (iii) lead to improved monitoring of response in drug and treatment trials
Keywords: 2-Hydroxy-N, N, N-trimethylethanaminium; 3-D; 3-Dimensional; Active Follow-up; activity marker; Acute; Address; Affect; Age; analog; Arts; Atrophic; Atrophy; blind; Blood - brain barrier anatomy; Blood-Brain Barrier; Body Tissues; Bone structure of cranium; Brain; Cells; Chiro-Inositol; Choline; Chronic; Clinical; clinical investigation; Clinical Trials; Clinical Trials, Unspecified; Clinical/Radiologic; Cognitive decline; Cognitive deficits; Cognitive Disturbance; cognitive dysfunction; Cognitive function abnormal; Cognitive Impairment; cognitive loss; cognitively impaired; cohort; Conflict; Conflict (Psychology); Corpus Callosum; Corpus Callosums; cranium; Cranium; Creatine; Crossmatching, Tissue; Development; Diagnostic; disability; Disease; disease severity; disease/disorder; Disorder; Disturbance in cognition; drug/agent; Drugs; Encephalon; Encephalons; Ethanaminium, 2-hydroxy-N, N, N-trimethyl-; Evaluation; Event; Evolution; Feedback; Fingerprint; follow-up; Future; Gender; Glycine, N-(aminoiminomethyl)-N-methyl-; gray matter; H+ element; Health; heavy metal lead; heavy metal Pb; Hemato-Encephalic Barrier; Histocompatibility Testing; histocompatibility typing; History; Hydrogen Ions; Image; imaging; Impaired cognition; Impairment; improved; Individual; Injury; Inositol; insular sclerosis; interest; Intermediary Metabolism; Investigators; language translation; Lead; Lesion; Link; Lipids; Location; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Spectroscopy; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Medication; Mesoinositol; Metabolic; Metabolic Processes; Metabolism; METBL; Methods; Methods and Techniques; Methods, Other; Metric; Microscopic; Modality; Molecular; Monitor; Motor; MR Imaging; MR Spectroscopy; MR Tomography; MRI; MRS; MRSI; MS (Multiple Sclerosis); MS Lesions; Multiple Sclerosis; Multiple Sclerosis Lesions; N-acetyl aspartate; N-acetyl-L-aspartate; N-acetylaspartate; Nature; Nerve Cells; Nerve Unit; Nervous System Diseases; nervous system disorder; Nervous System, Brain; Neural Cell; Neurocyte; Neurologic; Neurologic Disorders; Neurological; neurological disease; Neurological Disorders; neuronal; Neurons; Newly Diagnosed; NMR Imaging; NMR Tomography; novel; Nuclear Magnetic Resonance Imaging; Outcome; Pathogenesis; Pathology; Patients; Pb element; Pharmaceutic Preparations; Pharmaceutical Preparations; Protons; Recording of previous events; Relapse; Relative; Relative (related person); repair; repaired; Reporting; Research Personnel; Researchers; Resolution; response; Sclerosis, Disseminated; Severity of illness; Skull; Specificity; substantia alba; substantia grisea; Surrogate Markers; Symptoms; Techniques; Testing; Time; Tissue Crossmatchings; Tissue Typing; Tissues; tool; trait; Translating; Translatings; treatment trial; Virulence; Weight; white matter; Zeugmatography
Project start date: 2005-09-01
Project end date: 2011-05-31
Budget start date: 1-JUN-2009
Budget end date: 31-MAY-2011
5R01NS050520-05 (2009): $589173
SERIAL BRAIN 3D 1H MR SPECTROSCOPY IN MULTIPLE SCLEROSIS.
Gonen Oded, Professor Or Radiology And Neu
New York University School Of Medicinecity: New York country: United States (us)
Grant 2R56NS050520-06A1 from National Institute Of Neurological Disorders And Stroke
Keywords: 3-Dimensional; Acute; Address; Affect; American; Atrophic; base; blind; Blood - brain barrier anatomy; Brain; Cells; Characteristics; Choline; Chronic; Chronology; Clinical; Clinical Trials; Cognitive deficits; cohort; Conflict (Psychology); Corpus Callosum; cost; Creatine; Degenerative Disorder; Demyelinations; Deterioration; Development; Diagnosis; Diagnostic; disability; Disease; drug development; Edema; Event; follow-up; Future; Gliosis; Goals; gray matter; Health; Healthcare; Histocompatibility Testing; improved; Individual; Injury; Inositol; interest; Lead; Lesion; Link; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolic; Metabolism; Methods; Metric; Microscopic; Modality; Molecular; Monitor; motor deficit; Multiple Sclerosis; Multiple Sclerosis Lesions; N-acetylaspartate; Nature; Neurologic; Neurologic Examination; Neurons; Outcome; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Protons; Relapsing-Remitting Multiple Sclerosis; repaired; Reporting; Resolution; response; Severity of illness; Specificity; standard of care; success; Surrogate Markers; Testing; therapy development; Time; Tissues; tool; treatment trial; Weight; white matter
Relevance: We propose to continue a 5 year semi-annual follow-up of a cohort of 25 ‘recently diagnosed’ multiple sclerosis patients (a neurological degenerative disease affecting over 400,000 Americans and representing a $5 Billion healthcare burden) and 25 matched controls with quantitative MRI and three-dimensional multi-voxel MR spectroscopy. The goals are to identify and characterize non-invasive MR markers that will correspond to these each patient’s clinical status and will detect/predict its changes and deterioration faster than the current standard of care neurological examination. Success will enable clinicians to manage the disease of individual patients better and to streamline clinical trials (less subjects for shorter periods) with better secondary markers, thereby improving patient outcome and lowering the cost of MS treatment and drug developments
Project start date: 2005-09-01
Project end date: 2012-08-31
Budget start date: 30-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-10-067
2R56NS050520-06A1 (2011): $585927