BRAIN CHEMISTRY BY MR SPECTROSCOPIC IMAGING

Peter B Barker, Associate Professor
Hugo W. Moser Res Inst Kennedy Krieger Kennedy Krieger, Inc. Baltimore, Md 21205

Grant 5P41RR015241-040002 from National Center For Research Resources, IRG: ZRG1

Keywords: biomedical resource, brain imaging /visualization /scanning, chemistry, bioimaging /biomedical imaging, clinical research, nuclear magnetic resonance spectroscopy

Project start date: 2004-09-01

Project end date: 2005-08-31

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In Vivo Determination Of NAAG In Brain

Peter B Barker, Professor
Radiology And Radiological Sciencesjohns Hopkins University

Grant 1R21MH082322-01A1 from National Institute Of Mental Health, IRG: NPAS

Abstract: N-acetylaspartylglutamate (NAAG) is the most abundant peptide in the human brain. Levels of NAAG have been suggested to be abnormal in patients with disorders such as schizophrenia and amyotrophic lateral sclerosis, amongst others. Until recently, there were no means available for the non-invasive determination of brain NAAG levels. Conventional in vivo proton magnetic resonance spectroscopy has been frequently used to measure the combined resonance of NAAG and N-acetylaspartate (NAA), but it has only limited ability to separately detect the individual components, NAAG and NAA, because of their structural and spectral similarity. We have recently demonstrated that; (a) at field strengths of 3 Tesla, it is possible to use spectral editing techniques to selectively detect NAAG (and NAA) with high specificity, and (b) at very high magnetic field strength (e.g. 7 Tesla for human brain) and with sufficient homogeneity, it is possible to resolve NAA and NAAG directly using proton MR spectroscopic imaging (MRSI). In this pilot R21 application, we propose to further develop and validate methods for NAAG detection and quantitation at both 3 and 7T, and to apply these techniques to a pilot study of patients with schizophrenia at 3T. Regional NAAG levels in 20 patients will be measured and compared to age- and sex-matched normal control subjects. It is expected that this R21 project will provide preliminary data for subsequent, larger studies that will fully elucidate the role of NAAG in schizophrenia. N-acetylaspartylglutamate (NAAG) is the most abundant peptide in the brain, and is believed to play a central role in the pathogenesis of many cerebral disorders, including schizophrenia, amyotrophic lateral sclerosis, and others. Until recently, there was no direct way of measuring NAAG in the intact human brain. We have developed a new method for measuring NAAG using magnetic resonance spectroscopy (MRS). The purpose of this R21 grant is to extend this technique and map the spatial distribution of NAAG in the brain using MR spectroscopic imaging on high field scanners. The techniques developed will be applied to a pilot study of NAAG levels in patients with schizophrenia. In the long term, this research may lead to a better understanding of schizophrenia and treatment approaches

Project start date: 2008-12-04

Project end date: 2010-11-30

Proton MRSI Of Human Breast Cancer At 3 And 7 Tesla

Peter B Barker, Professor
Radiology And Radiological Sciencesjohns Hopkins University

Grant 5R01CA125258-02 from National Cancer Institute, IRG: MEDI

Abstract: Breast cancer is the most common form of cancer in women. In the year 2004, it was estimated that approximately 217,000 new cases of breast cancer were diagnosed in the United States, and that 40,000 deaths were attributed to the disease. The key to successful treatment of breast cancer is early diagnosis, and the use of widespread mammography screening has resulted in significant improvements in breast cancer survival rates. However, a major problem with mammography is a lack of specificity; in some studies, as many of 70-80% of suspicious lesions on mammography referred for biopsy ultimately have a benign final diagnosis. These ´unnecessary" biopsies represent a significant economic burden on health care systems, and are also invasive and unpleasant for the patient. Therefore, there is a need for the development of new non-invasive, cost-effective, and safe diagnostic imaging procedures with enhanced specificity and sensitivity. Proton MR spectroscopic imaging (MRSI) is a non-invasive metabolic imaging technique that shows promise for the non-invasive diagnosis of human breast cancer. Preliminary data from our group and others suggests that an elevated choline signal (detected in the proton MR spectrum) is a marker of malignant breast disease. However, the low signal-to-noise ratio of proton MRSI currently limits this methodology to quite large lesions (e.g. 1 cm or greater), and makes detection of small Cho signals difficult. Also, few previous studies have investigated the spatial distribution of Cho in breast cancer lesions. In this proposal, we therefore propose to develop methods for MRSI on high field MR systems (3 and 7 Tesla) that are expected to exhibit higher sensitivity and resolution than lower field scanners. Methods will be developed for full breast coverage at high magnetic fields in short scan times, using phased-array receiver coils, and optimal water and lipid suppression. Methods will also be developed for the quantitative determination of lesion choline concentrations. These methods will be developed in years 1 and 2, and, in years 3 through 5, the clinical value of MRSI will be investigated. Specifically, choline levels will be compared between histologically defined tissue types (malignant and benign), in patients who are scheduled for breast biopsy. The sensitivity and specificity of proton MRSI in this patient group will be determined, and compared between field strengths. In addition, the diagnostic value of MRSI will be compared to that of conventional MRI in the same population

Project start date: 2007-08-08

Project end date: 2012-07-31

1R01CA125258-01A1 (2007): $398775

Proton MR Spectroscopic Imaging In Human Breast Cancer

Peter B Barker, Associate Professor
Radiology And Radiological Sciencesjohns Hopkins University
w400 Wyman Park Building
baltimore, Md 212182680

Grant 1R21CA091798-01 from National Cancer Institute, IRG: ZCA1

Abstract: Breast cancer is the most common form of cancer in women. In the year 2000, it is predicted that approximately 180,000 new cases of breast cancer will be diagnosed in the United States, and 40,000 women will die from the disease. The key to successful treatment of breast cancer is early diagnosis, and the use of widespread mammography screening has resulted in significant improvements in breast cancer survival rates. However, a major problem with mammography is a lack of specificity; 70-80% of suspicious lesions on mammography referred for biopsy ultimately have a benign final diagnosis. These "unnecessary" biopsies represent a significant economic burden on health care systems, and are also invasive and unpleasant for the patient. Therefore, there is a need for the development of new non-invasive, cost-effective, and safe imaging procedures with enhanced specificity and sensitivity. Proton MR spectroscopic imaging (MRSI) is a non-invasive metabolic imaging technique, which has yet to be applied to human breast cancer. Preliminary data from our group and others, based on cell preparations, in vitro studies and single-voxel human spectroscopy, suggest that an elevated composite choline signal (detected in the proton MR spectrum) is a marker of malignant breast disease. Benign lesions and normal breast tissue have little or no detectable choline signal. However, technical developments are required before proton MRSI can become a clinical procedure for evaluating breast cancer. These include maximizing spatial resolution, optimizing water and lipid suppression techniques, development of quantitation methodology, and providing whole breast coverage within a clinically acceptable scan time. We will develop and test these techniques in years one and two of this proposal (phase I, R21), and in years 3 and 4 (phase II, R33) we will apply these techniques to a trial of proton MRSI in human breast cancer. Specifically, choline levels will be compared between histologically defined tissue types, in patients who are scheduled for breast biopsy. The sensitivity and specificity of proton MRSI in this patient group will be determined. The techniques developed in this proposal will also assist in the translation of proton MRSI to other organ systems and pathologies, and increase the acceptance of clinical proton MRSI as a diagnostic imaging modality

Keywords: breast neoplasm, diagnosis design /evaluation, mammography, nuclear magnetic resonance spectroscopy choline, method development clinical research, female, human subject, women`s health

Project start date: 2001-09-01

Project end date: 2003-08-31

1R21CA091798-01 (2001): $158978

5R33CA091798-04 (2005): $279381

4R33CA091798-03 (2004): $272973