HIGHER SPEED FIELD & SPATIAL RESOLUTION BRAIN 3D PROTON
Oded Gonen, Professor
Fox Chase Cancer Center
333 Cottman Avenue
philadelphia, Pa 191112434
Grant 2R01NS033385-04 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: Verbatim from ´s ) During the past few years, numerous in vivo brain proton (1H) magnetic resonance spectroscopy (MRS) Studies have suggested a correlation between pathology and the observable metabolite levels in cancer, epilepsy, Alzheimer´s disease, multiple sclerosis, HIV infection, stroke and other disorders of the central nervous system. Unfortunately 1H-MRS still suffers from (a) low voxel signal-to-noise ratio at the desired, sub 1 ml, spatial resolution obtained at a "clinically reasonable" 40 min. session; (b) spectral contamination by signals from extraneous tissue, due to limitations of current localization methods, especially at high, >3 Tesla, magnetic fields; and (c) scarcity of software to design and interpret results from these experiments. To address these, the first goal of this project is to develop and optimize echo and non-echo 3D localization methods based exclusively on Hadamard spectroscopy imaging (HIS). Using 3D HIS in all directions with either surface or volume-coils will (a) improve the voxels´ profile, hence, intervoxel isolation; (b) intrinsically suppress extraneous contamination; (c) be simple to implement, post-process and display; (d) be suitable for 1H-MRS even at very high, >3 T, magnetic fields, i.e., immune to the chemical shift artifacts associated with selective-pulses; and (e) require fewer encoding steps, thus, execute faster than chemical-shift-imaging based methods. The second goal is to produce platform-independent image-guided radio-frequency pulse-design and data post-processing software for the first goal. The purpose and guiding philosophy is to ensure that the deliverables from this project pulse-timing sequence templates, pulse design tools, post processing and display software, can be straightforwardly implemented on any modern imager and computing platform. This work will extend both the clinical and biomedical research applications of 1H-MRS by providing increased spatial resolution, shorter acquisition time and 3D localization sequences suited for clinical, <2 Tesla, as well as high, >3 T, magnetic fields. The development will support ongoing studies investigating changes in brain metabolites associated with multifocal and diffuse brain disorders, specifically, multiple-sclerosis, aging, brain trauma, AIDS and pediatric neurodegenerative diseases
Keywords: biomedical equipment development, brain visualization, clinical biomedical equipment, nuclear magnetic resonance spectroscopy computer data analysis, diagnosis design /evaluation, image processing, noninvasive diagnosis bioimaging /biomedical imaging, clinical research, human subject
Project start date: 1996-07-22
Project end date: 2002-04-30
2R01NS033385-04 (1999): $3
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Oded Gonen
Neuroimaging Of MS - State Of The Art And Future Directions
Oded Gonen, Professor
Radiologynew York University School Of Medicine
Grant 1R13NS065551-01 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: The conference we propose is entitled "Neuroimaging of MS - State-of-the-art and Future Directions" and will be held on Friday and Saturday, November 6 and 7, 2009 in Washington DC. This conference is relevant to the missions of both the NINDS and NIBIB. The target audience is interdisciplinary PhD and MD (radiology and neurology) experts in the fields of multiple sclerosis (MS) imaging and management. MS is a chronic disease afflicting the central nervous system (CNS) of young adults and can last decades. MR methods therefore are ideally suited for its study due to their ability to image non-invasively CNS tissue, metabolism and function. MS is studied by PhD´s who develop imaging technologies, neuro-radiologists who apply them and neurologists who treat the patients and design treatment trials. This conference is designed, therefore, (1) to acquaint these three diverse groups with the current state-of-the-art MR technology for MS; (2) to identify the techniques that are most likely to become suitable for routine clinical application; and (3) to reach a consensus as to which critical steps are needed to expedite and foster this translation. This would ultimately result in improved care and outcomes for a greater number of MS patients (400,000 currently in the US and 2.5 million worldwide). The conference will span two days. The first day will consist of a series of overview presentations introducing the current state-of-the-art MR imaging of the brain and spine in MS and then focus on the clinical applications in this disease. The second day will commence with one additional series of overview presentations focusing on the current "most ambitious "art, followed by three concurrent workshops. Each workshop will be offered twice to enable attendees to participate in more than one. The workshops will each discuss one of the three most advance imaging modalities - "Molecular imaging", "Quantitative MRI" and "MR at the extremes" (high magnetic fields, difficult CNS regions). For each of the three areas addressed, three sets of recommendations will be clearly stated at the end 1) Which method(s) is/are most likely to be ready for clinical use within the next 5 years. 2) What the researchers should do to help address the issues raised during the discussions regarding that topic in order to expedite this transition; and 3) what could the NIH do in terms of requests for applications (RFAs). These recommendations will constitute the core of the proceedings from the meeting, and will be published concurrently in the American Journal of Neuroradiology and in Multiple Sclerosis. The organizing committee endeavored to ensure a diversity among the invited speakers who comprise a mix of established and junior clinical and research scientists from various geographic regions in North America and Europe. Selection of invited junior scientists for whom funding is requested was merit based. The three goals of the conference are (1) to acquaint MS researchers and clinicians of different disciplines (PhDs, neuroradiologists and neurologists) with the state-of-the-art MR methodology in multiple sclerosis; (2) to reach a consensus which of these methodologies is both needed and is mature enough (in the laboratory) for translation into the clinical environment; and (3) to determine what is needed to standardize these "ready" methodologies to foster and expedite this translation. The outcome will be coherent focused progress that will benefit a greater number of MS patients, sooner and ultimately result in improved care and management for the 400,000 MS patients in the US and the over 2.5 million patients worldwide
Project start date: 2009-07-01
Project end date: 2010-06-30
NON ECHO PROTON SPECTROSCOPY W/ HADAMARD SPECTROSCOPIC IMAGING
Oded Gonen, Professor
Institution:
Grant 5P41RR002305-130038 from National Center For Research Resources
Abstract: One of the main problems in proton in-vivo spectroscopy is to reduce the strong fat signal. To do this a combination of fat suppression and echo spectroscopy are commonly used. However, due to the short T2 of some of the proton spectral lines and their different J-coupling constants, any choice of an echo time that fits one of the spectral lines results in loss of signal intensity and the observation of phase distortions in all other spectral lines. We propose to use the special properties of the Hadamard encoding localization method to obtain proton non-echo spectroscopy and two approaches are being used. The first is longitudinal Hadamard encoding. We use the excellent slice profile of adiabatic inversion pulses to Hadamard encode only spins within the brain without the fat spins. We have shown that two orders of magnitude fat signal reduction is achieved with these pulses. Together with outer volume suppression, the fat signal is sufficiently suppressed. We have demonstrated experimentally on phantom samples the possibility of fat suppression with longitudinal Hadamard encoding. In vivo human experiments are currently being performed. The second approach is transverse Hadamard encoding. In this approach we use the selective excitation profile of the transverse Hadamard encoding together with the fat suppression achieved by the Hadamard transformation. Experiments on phantom samples demonstrate three order of magnitude fat suppression. Together with outer volume suppression, this is sufficient for in-vivo experiments. Experiments in-vivo and comparison between the two approaches are currently being performed.
HIGHER SPEED, FIELD AND SPATIAL RESOLUTION BRAIN 3D 1H MRS
Oded Gonen, Professor Or Radiology And Neu
New York University School Of Medicine, New York, Ny 10016
Grant 5R01EB001015-15 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: AIDS Virus; Accessory Bodies of Cajal; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Address; Algorithms; Alzheimer; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer`s; Alzheimer`s Disease; Alzheimers Dementia; Alzheimers disease; Anatomic; Anatomical Sciences; Anatomy; Apoplexy; Artifacts; B7-1; BB1; Body Tissues; Bone structure of cranium; Brain; CD28LG; CD28LG1; CD80; CD80 gene; Cancers; Cell Communication and Signaling; Cell Signaling; Central Nervous System; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cerebrovascular accident; Cervical Vertebrae; Cervical spine; Characteristics; Chemical Shift Imaging; Chemicals; Clinical Research; Clinical Study; Coiled Bodies; Color; Computer Programs; Computer software; Coupled; Cranium; Data; Data Set; Dataset; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Deposit; Deposition; Detection; Development; Disease; Disorder; Effectiveness; Encephalon; Encephalons; Epilepsy; Epileptic Seizures; Epileptics; Frequencies (time pattern); Frequency; Funding; Goals; H+ element; HIV; HTLV-III; Heating; Human; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human, General; Hybrids; Hydrogen Ions; Idiopathic Parkinson Disease; Image; Imagery; Intermediary Metabolism; Intracellular Communication and Signaling; LAB7; LAV-HTLV-III; Lead; Lewy Body Parkinson Disease; Link; Lipids; Lymphadenopathy-Associated Virus; METBL; MR Imaging; MR Spectroscopy; MR Tomography; MRI; MRS; MRSI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Manufacturer; Manufacturer Name; Maps; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Mental disorders; Mental health disorders; Metabolic; Metabolic Processes; Metabolism; Methods; Methods and Techniques; Methods, Other; Monitor; Morphologic artifacts; NMR Imaging; NMR Tomography; Nervous System Diseases; Nervous System, Brain; Nervous System, CNS; Neuraxis; Neurologic; Neurologic Disorders; Neurological; Neurological Disorders; Noise; Nuclear Magnetic Resonance Imaging; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson`s; Parkinson`s disease; Parkinsons disease; Pattern; Pb element; Performance; Physiologic pulse; Predisposition; Primary Parkinsonism; Primary Senile Degenerative Dementia; Process; Proliferating; Protons; Psychiatric Disease; Psychiatric Disorder; Pulse; Radio; Recycling; Relaxation; Research; Resolution; Scheme; Science of Anatomy; Seizure Disorder; Signal Transduction; Signal Transduction Systems; Signaling; Skull; Slice; Software; Spatial Distribution; Spectroscopy; Spectrum Analyses; Spectrum Analysis; Speed; Speed (motion); Spinal Column; Spine; Steam; Stroke; Sum; Surface; Susceptibility; Techniques; Technology; Testing; Thick; Thickness; Time; Tissues; Translating; Translatings; Translations; Trauma; Uncertainty; Unspecified Mental Disorder; Vascular Accident, Brain; Vertebral column; Virus-HIV; Visualization; Zeugmatography; anatomy; backbone; base; biological signal transduction; brain attack; brain volume; cerebral vascular accident; computer program/software; cranium; dementia of the Alzheimer type; disease/disorder; doubt; epilepsia; epileptiform; epileptogenic; experiment; experimental research; experimental study; falls; heavy metal Pb; heavy metal lead; human subject; image processing; imaging; improved; in vivo; instrument; interest; language translation; magnetic field; malignancy; mental illness; neoplasm/cancer; nervous system disorder; neurological disease; novel; primary degenerative dementia; psychological disorder; research study; response; senile dementia of the Alzheimer type; stroke; tool; volunteer
Project start date: 1996-07-22
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
5R01EB001015-15 (2010): $637345
5R01EB001015-14 (2009): $635016
2R01EB001015-13A2 (2008): $598897
SIMULTANEOUS 3D MULTIVOXEL LOCAL PROTON NMR SPECTROSCOPY OF IN VIVO HUMAN BRAIN
Oded Gonen, Professor
Institution:
Grant 5P41RR002305-130039 from National Center For Research Resources
Abstract: Localized, multivoxel 1H spectroscopy (MRS) of in vivo human brain is currently of great interest. To increase the efficiency of commonly used CSI techniques we develop 3D coverage of the volume-of-interest (VOI), which excites and observes the spins in the entire volume every acquisition. Therefore, R(N) SNR gain per given measurement time is expected over the current method of sequential interleaving N 2D slices. 3D coverage is achieved with a hybrid of chemical shift imaging (CSI) and transverse Hadamard spectroscopic imaging (HSI) to obtain 3D, multivoxel arrays of voxels in a Siemens SP63 imager in ~25 min. CHESS water suppression was followed by outer-volume-suppression of the fat signals and selective-excitation of an axial, slab-likeVOI. The spatially-selective HSI-encoding RF pulses incorporate naturally into the PRESS double spin-echo sequence used to excite the VOI selectively. This VOI accommodates few partitions along its short axis (hence the use of HSI) and many partitions along the other long axes, hence use of CSI in the hybrid. The 3D hybrid was performed on a volunteer. A 16x16x4 localization matrix in an 8x8x4 cm PRESS VOI yielded 1 ml voxels. The MRS took 25 min. and the entire session 1 hour. For comparison, a 27 min., 4 slice interleaved MRS was performed immediately afterwards without moving the volunteer or changing the imager settings. Spectra from the slice overlapping showed that (as expected) the SNR is ~twofold better than the spectra from interleaves slices for each of the 1H spectral lines. This is a result of the entire examination time available to all the slices in the hybrid, versus only N-1 of it for the interleaved.
Serial Brain 3D 1H MR Spectroscopy In Multiple Sclerosis
Oded Gonen, Professor
New York University School Of Medicine New York, Ny 10016
Grant 5R01NS050520-03 from National Institute Of Neurological Disorders And Stroke IRG: MEDI
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: brain imaging /visualization /scanning, multiple sclerosis, brain disorder diagnosis, brain metabolism, diagnosis design /evaluation, gray matter, prognosis, white matter, bioimaging /biomedical imaging, clinical research, human subject, nuclear magnetic resonance spectroscopy, patient oriented research, three dimensional imaging /topography
Project start date: 2005-09-01
Project end date: 2010-05-31
5R01NS050520-03 (2007): $571999
5R01NS050520-02 (2006): $571921
1R01NS050520-01A1 (2005): $483638
DEVELOPMENT OF ADVANCED CHEMICAL SHIFT IMAGING (CSI) TECHNIQUES
Oded Gonen, Professor
Fox Chase Cancer Center 333 Cottman Avenue Philadelphia, Pa 191112434
Grant 2P01CA041078-100006 from National Cancer Institute
Abstract: Chemical Shift Imaging (CSI) is the method of choice for in vivo localized spectroscopy. However, several persistent obstacles still remain in its application to nuclei other than protons, specifically 31P and 19F CSI proposed in projects of this application. First, the sensitivity is low. Second and several consequents, the measurements are long, thus, only one nucleus can be observed in a clinical session, even if information from another is significant and sought. Third, the current Fourier reconstruction methods, widely used because of their computational convenience and simplicity, result in an artifact that intermixes signal from one voxel, with its its neighbors. This artifact, known as A voxel bleed, leads to spectral-contamination and impacts CSI in general. We propose to address these difficulties from three angles. First, to use polarization transfer techniques from 1H to the less sensitive 31P to increase the signal of the latter and to be used in project II. Second, to develop simultaneous acquisition techniques that will allow 1H decoupled 31P and 19F CSI acquisition during a single clinical examination. Third, to develop non-Fourier transform techniques that, using prior knowledge from the proton images, will improve the accuracy of CSI reconstruction.
Keywords: diagnosis design /evaluation, image enhancement, method development, neoplasm /cancer diagnosis, nuclear magnetic resonance spectroscopy, brain neoplasm, head /neck neoplasm, squamous cell carcinoma, clinical research, human subject
Project start date: 1998-04-01
Project end date: 1999-03-31
Sponsored Links Excellgen http://Excellgen.com
HIGHER SPEED, FIELD & SPATIAL RESOLUTION BRAIN 3D 1H MRS
Oded Gonen, Professor
New York University School Of Medicine New York, Ny 10016
Grant 5R01EB001015-12 from National Institute Of Biomedical Imaging And Bioengineering IRG: ZRG1
Abstract: Changes in metabolic levels observed with proton-magnetic-resonance-spectroscopy ( H-MRS) are frequently used to augment the highly sensitive (but not specific) MRI. At 1.5 Tesla, MRS has so far linked anatomy from MRI with the underlying metabolism in cancer, epilepsy, Alzheimer s disease, multiple sclerosis, HIV infection, stroke and other disorders of the central nervous system (CNS). Therefore, it was anticipated that high-magnetic-field (Bo ) 1.5 T) imagers would provide H-MRS a much needed boost in sensitivity. Unfortunately, that has not happened Translating the most useful 2 and 3 dimensional (3D) H-MRS techniques to high-Bos has been stymied by high radio-frequency (BI) power requirements; short TZ reducing the signal-to-noise-ratio (SNR) gain; chemical shift misregistration errors; and scarcity of software to shim, design 3D localization, evaluate and display the large 3D MRS data sets. The long term goal of this competing continuation is to develop and implement 30 H-MRS methods to address the above issues and perform better at higher BG. They will be extensions of the hybrid techniques developed in the past two cycles. Specific Aim 1 will exploit the shorter T2s for (a) 3D coverage by optimal interleaving of "slabs," across the volume-of-interest, each thin enough to excite with the available B1 under strong gradients to minimize the misregistration error; and (b) increase the spatial resolution to ((1 ~m )~voxels, and extend coverage all the way to the skull. Specific Aim 2 will introduce 3D localization into our non-echo, non-localized, whole head H-MRS, to provide a rapid, imager-side, lower-resolution "metabolic localizer." Specific Aim 3 will utilize the increased sensitivity to produce very high spatial resolution, (0.5 - 0.375 ~m )~ voxels, in restricted regions, e.g., the optic nerve or spinal cord, both of which are currently inaccessible. Finally, Specific Aim 4 will develop novel methods to detect and visualize relationships between different metabolites spatial distributions to simplify the staggering, often confusing, amount of information generated by 3D H MRS. The health relatedness of this project is its extension of increased spatial resolution, volume covered and shorter acquisition time 3D H-MRS methods to high, 23 T, magnetic fields, to support ongoing and future studies of CNS metabolism associated with multifocal and diffuse diseases.
Project start date: 1996-07-22
Project end date: 2008-08-31
5R01EB001015-12 (2006): $774835
3R01EB001015-11S1 (2005): $185478
5R01EB001015-11 (2005): $593467
5R01EB001015-10 (2004): $597283
5R01EB001015-09 (2003): $582021
9R01EB001015-08 (2002): $581967
Quantifying Radiation-Therapy Brain Injury With 1H-MRS
Oded Gonen, Professor
New York University School Of Medicine New York, Ny 10016
Grant 5R21CA092547-02 from National Cancer Institute IRG: ZRG1
Abstract: Brain metastases present in 50-80 percent of small-cell-lung-cancer (SCLC) survivors within two years. To reduce this risk and improve their outcome, prophylactic-cranial-irradiation (PCI) is now offered to certain SCLC patients even in the absence of distinct visible brain pathology. Although neurotoxicity is always a concern in brain radiation-therapy (RT), there is currently no direct method to quantify its damage to the central nervous system (CNS). Such knowledge is critical for (a) risk/benefit assessment; and (b) dose determination. Presently, such damage can only be assessed indirectly, using neurocognitive tests. Unfortunately, the results of such tests are often confounded by other factors such as language barriers, patients state of mind and/or their level of fatigue, fear and depression. Clearly, an objective, i.e., preferably instrumental, non-invasive and, most importantly, sensitive method to quantify RT neurotoxicity is necessary. We propose to quantify the extent of neurona1 cell loss imparted to the brain by RT through the decline of the amino acid derivative N-acetylaspartate (NAA) using state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Since NAA is believed to be present in neuronal cells only, its amount is proportional to their number and/or integrity. Consequently, we will obtain the amount of whole-brain-NAA (WBNAA) in 40 patients pre, immediately post- (2-3 weeks later) and six months after whole-brain radiation-therapy (WBRT). Since we will evaluate the amount of NAA in the entire brain, its signal-to-noise-ratio (SNR) will be excellent, facilitating short, < 15 min. examinations. It will also not be susceptible to misregistration errors that currently beset serial studies, nor will it be sensitive to the local transient edema common in WBRT. The WBNAA measurements will be augmented by the current tool used to evaluate CNS injury - the mini-mental status examination (MMSE) for correlation and comparison. We will use these observations to test the following three hypotheses, H1- H3 H1 That WBRT induces neuronal injury quantifiable with WBNAA in these patients. H2 That WBNAA is more sensitive than MMSE to detect neuronal injury consequences of WBRT. H3 That this neuronal injury may be transient, in part, and could resolve within several months after WBRT.
Keywords: brain disorder diagnosis, brain injury, neoplasm /cancer radiation therapy, noninvasive diagnosis, therapy adverse effect, aspartate, brain, disease /disorder prevention /control, longitudinal human study, metastasis, nervous system regeneration, neuron, neurotoxicology, small cell lung cancer, adult human (21+), clinical research, human subject, hydrogen ion, nuclear magnetic resonance spectroscopy, patient oriented research, psychological test
Project start date: 2002-07-03
Project end date: 2006-06-30
5R21CA092547-02 (2003): $211146
NON ECHO, 3-D LOCALIZED, BRAIN PROTON NMR SPECTROSCOPY
Oded Gonen, Professor
Fox Chase Cancer Center 333 Cottman Avenue Philadelphia, Pa 191112434
Grant 5R01NS033385-03 from National Institute Of Neurological Disorders And Stroke IRG: ZRG7
Abstract: Adapted from Applicant s ) Localized NNR spectroscopy (MRS) of observable brain proton (1H) metabolites levels is currently used in many centers for non-invasive studies of tumors, stroke, HIV infection, multiple sclerosis, and Alzheimer disease. To cover a significant portion of the brain; current 1H MRS techniques interleave 2-D slices, each measured separately by a spin-echo sequence. Unfortunately, interleaving is an inefficient use of the limited clinical examination time, and the spin-echo delays cause T1-weighting and J-coupling modulations of the signals. Consequently the observed metabolite levels depend on the particular localization scheme used and the sensitivity is relatively low considering that the variation in these pathologies are less than 30 percent. s proposed to address the issues of low sensitivity and sequence-dependence by developing 3-D localization methods using combinations (hybrids) of two non-echo, multivoxel 1H MRS techniques Chemical Shift Imaging (CSl) with Hadamard Spectroscopic Imaging (HS1). Three significant benefits could be realized. First, per equal measurement time, 3-D hybrids will result in a two to three fold gain in sensitivity over 2-D interleaved acquisition (depending on whether 4 or 8 slices are sought). Second, because the hybrids are non-echo, the J- coupling modulation artifacts and T2 losses will be minimal, yielding another 25 to 50 percent of sensitivity. Combined, the overall three to five fold increase will provide a dramatic boost to the reliability of metabolite level evaluation. Third, because the development will result in software to generate optimized pulse sequences, the methods could be implemented on any imager capable of producing shaped pulses. Since expensive, fast shielded-gradients are not intrinsically required, the proposed research will make multivoxel brain 1H MRS accessible to sites not yet equipped with them.
Keywords: biomedical equipment development, brain visualization, clinical biomedical equipment, nuclear magnetic resonance spectroscopy, diagnosis design /evaluation, image processing, noninvasive diagnosis, clinical research, human subject
Project start date: 1996-07-22
Project end date: 2000-04-30
5R01NS033385-03 (1998): $291969
HIGHER SPEED, FIELD & SPATIAL RESOLUTION BRAIN 3D 1H MRS
Oded Gonen, Professor
Fox Chase Cancer Center
333 Cottman Avenue
philadelphia, Pa 191112434
Grant 5R01NS033385-06 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: Adapted from Applicant´s ) Localized NNR spectroscopy (MRS) of observable brain proton (1H) metabolites levels is currently used in many centers for non-invasive studies of tumors, stroke, HIV infection, multiple sclerosis, and Alzheimer´ disease. To cover a significant portion of the brain; current 1H MRS techniques interleave 2-D slices, each measured separately by a spin-echo sequence. Unfortunately, interleaving is an inefficient use of the limited clinical examination time, and the spin-echo delays cause T1-weighting and J-coupling modulations of the signals. Consequently the observed metabolite levels depend on the particular localization scheme used and the sensitivity is relatively low considering that the variation in these pathologies are less than 30 percent. s proposed to address the issues of low sensitivity and sequence-dependence by developing 3-D localization methods using combinations (hybrids) of two non-echo, multivoxel 1H MRS techniques Chemical Shift Imaging (CSl) with Hadamard Spectroscopic Imaging (HS1). Three significant benefits could be realized. First, per equal measurement time, 3-D hybrids will result in a two to three fold gain in sensitivity over 2-D interleaved acquisition (depending on whether 4 or 8 slices are sought). Second, because the hybrids are non-echo, the J- coupling modulation artifacts and T2 losses will be minimal, yielding another 25 to 50 percent of sensitivity. Combined, the overall three to five fold increase will provide a dramatic boost to the reliability of metabolite level evaluation. Third, because the development will result in software to generate optimized pulse sequences, the methods could be implemented on any imager capable of producing shaped pulses. Since expensive, fast shielded-gradients are not intrinsically required, the proposed research will make multivoxel brain 1H MRS accessible to sites not yet equipped with them
Keywords: biomedical equipment development, brain imaging /visualization /scanning, clinical biomedical equipment, nuclear magnetic resonance spectroscopy computer data analysis, diagnosis design /evaluation, image processing, noninvasive diagnosis bioimaging /biomedical imaging, clinical research, human subject
Project start date: 1996-07-22
Project end date: 2001-05-31
5R01NS033385-06 (2001): $423306
Sponsored Links Excellgen http://Excellgen.com
5R01NS033385-05 (2000): $1
NON ECHO, 3-D LOCALIZED, BRAIN PROTON NMR SPECTROSCOPY
Oded Gonen, Professor
Fox Chase Cancer Center
333 Cottman Avenue
philadelphia, Pa 191112434
Grant 5R01NS033385-02 from National Institute Of Neurological Disorders And Stroke IRG: ZRG7
Abstract: Adapted from Applicant´s ) Localized NNR spectroscopy (MRS) of observable brain proton (1H) metabolites levels is currently used in many centers for non-invasive studies of tumors, stroke, HIV infection, multiple sclerosis, and Alzheimer´ disease. To cover a significant portion of the brain; current 1H MRS techniques interleave 2-D slices, each measured separately by a spin-echo sequence. Unfortunately, interleaving is an inefficient use of the limited clinical examination time, and the spin-echo delays cause T1-weighting and J-coupling modulations of the signals. Consequently the observed metabolite levels depend on the particular localization scheme used and the sensitivity is relatively low considering that the variation in these pathologies are less than 30 percent. s proposed to address the issues of low sensitivity and sequence-dependence by developing 3-D localization methods using combinations (hybrids) of two non-echo, multivoxel 1H MRS techniques Chemical Shift Imaging (CSl) with Hadamard Spectroscopic Imaging (HS1). Three significant benefits could be realized. First, per equal measurement time, 3-D hybrids will result in a two to three fold gain in sensitivity over 2-D interleaved acquisition (depending on whether 4 or 8 slices are sought). Second, because the hybrids are non-echo, the J- coupling modulation artifacts and T2 losses will be minimal, yielding another 25 to 50 percent of sensitivity. Combined, the overall three to five fold increase will provide a dramatic boost to the reliability of metabolite level evaluation. Third, because the development will result in software to generate optimized pulse sequences, the methods could be implemented on any imager capable of producing shaped pulses. Since expensive, fast shielded-gradients are not intrinsically required, the proposed research will make multivoxel brain 1H MRS accessible to sites not yet equipped with them
Keywords: biomedical equipment development, brain visualization, clinical biomedical equipment, nuclear magnetic resonance spectroscopy diagnosis design /evaluation, image processing, noninvasive diagnosis clinical research, human subject
Project start date: 1996-07-22
Project end date: 1999-04-30
5R01NS033385-02 (1997): $369701
SERIAL BRAIN 3D NMR SPECTROSCOPY IN MULTIPLE SCLEROSIS
Oded Gonen, Professor
Fox Chase Cancer Center
333 Cottman Avenue
philadelphia, Pa 191112434
Grant 5R01NS037739-03 from National Institute Of Neurological Disorders And Stroke IRG: ZRG7
Abstract: Adapted from Applicant´s ) Contrast-enhanced magnetic resonance imaging (MRI) is becoming increasingly important in the evaluation of multiple sclerosis (MS) based on its sensitivity to acute, often subclinical events in the brain and its ability to measure the accumulation of the disease over time. However, to date there are conflicting reports concerning the number and volume of these lesions, "the load of the disease" and the neurological severity. To resolve these conflicts, recent studies employed proton (1H) magnetic resonance spectroscopy (MRS) to investigate the lesions underlying metabolism. They showed that it may be possible to assess the irreversibility of central nervous system injury, discern between edematous and demyelination lesions and (perhaps) predict the time course of their evolution. However, these studies employed the current art of single voxel or small 2D arrays of few tens voxels, which, due to their limited observable volume(s) of interest, must be image-guided onto the pathologies of interest. This restricted them to the study of (i) MRI detectable existing lesions; and (ii) few foci in a single clinical session due to time and voxel-size constraints. s proposed to overcome both these problems with their new three dimensional (3D) 1H-MRS hybrids to achieve simultaneous coverage of most the white-matter volume in clinically feasible time ~45 min. The 3D hybrids yield ~1000 high resolution, <0.8 cm3 , voxels per exam from 0.5-0.75 liter of brain tissue. Such extensive coverage will enable us to examine (i) whether lesions develop in white matter regions which are already metabolically abnormal; and (ii) whether 1H-MRS-detected local metabolic changes, primarily neuronal loss in conjunction with demyelination, can predict the onset of a lesion before contrast-enhanced MRI, determining its type and course. These two hypotheses will be investigated by following cohort of 12 relapsing-remitting MS patients over three years with 3D 1H-MRS every 3 months. The MRS data will be compared with (i) localized 1H metabolic levels in age, sex and race matched healthy volunteers; (ii) the contrast enhanced MRI which they undergo every 6 months during that period; and (iii) their own previous local metabolic levels. The 1H-MRS data will be obtained both at the highest, 4 Tesla, magnetic field approved for human use, for maximal sensitivity and at the common clinical filed of 1.5 Tesla
Keywords: biomedical equipment development, brain metabolism, brain visualization, diagnosis design /evaluation, multiple sclerosis, nuclear magnetic resonance spectroscopy bioengineering /biomedical engineering, bioimaging /biomedical imaging, clinical research, human subject
Project start date: 1998-08-01
Project end date: 2001-05-31
5R01NS037739-03 (2000): $3
5R01NS037739-02 (1999): $3
NON ECHO, 3-D LOCALIZED, BRAIN PROTON NMR SPECTROSCOPY
Oded Gonen, Professor
Fox Chase Cancer Center
333 Cottman Avenue
philadelphia, Pa 191112434
Grant 1R01NS033385-01A3 from National Institute Of Neurological Disorders And Stroke IRG: ZRG7
Project start date: 1996-07-22
Project end date: 1999-04-30
1R01NS033385-01A3 (1996): $397857