Publications

1997
SS Yoo, CR Guttmann, JR Ives, LP Panych, R Kikinis, DL Schomer, and FA Jolesz. 1997. “3D localization of surface 10-20 EEG electrodes on high resolution anatomical MR images.” Electroencephalogr Clin Neurophysiol, 102, 4, Pp. 335-9.Abstract
A method to visualize surface EEG electrodes on conventional high-resolution magnetic resonance (MR) images is presented. Because conventional silver or gold electrodes generate an insignificant artifactual signal signature in MR images, a plastic capsule filled with gadolinium-doped water was designed to mold onto each electrode, thereby outlining the electrode surfaces as a negative imprint on MR images. MR images of the head with capsules affixed clearly demonstrated the location and shape of the electrodes. Selected cranial tissues were identified by using semi-automatic image segmentation to determine their three-dimensional spatial relationship to the electrodes. Such representations could be used as a starting point for more precise EEG source localization modeling applicable to individual patients.
MJ Hohol, CR Guttmann, J Orav, GA Mackin, R Kikinis, SJ Khoury, FA Jolesz, and HL Weiner. 1997. “Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.” Arch Neurol, 54, 8, Pp. 1018-25.Abstract
OBJECTIVE: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. SETTING: A research clinic of a university hospital. PATIENTS: Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. RESULTS: Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.
MJ Hohol, CR Guttmann, J Orav, GA Mackin, R Kikinis, SJ Khoury, FA Jolesz, and HL Weiner. 1997. “Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.” Arch Neurol, 54, 8, Pp. 1018-25.Abstract
OBJECTIVE: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. SETTING: A research clinic of a university hospital. PATIENTS: Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. RESULTS: Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.
1996
KR Bridges, GD Barabino, C Brugnara, MR Cho, GW Christoph, G Dover, BM Ewenstein, DE Golan, CR Guttmann, J Hofrichter, RV Mulkern, B Zhang, and WA Eaton. 1996. “A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy.” Blood, 88, 12, Pp. 4701-10.Abstract
During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.
K Oshio, LP Panych, and CR Guttmann. 1996. “A simple noninvasive stereotactic device for routine MR head examinations.” J Comput Assist Tomogr, 20, 4, Pp. 588-91.Abstract
A simple device to define reproducible reference points in MR examinations was designed. The device can be worn like a pair of eyeglasses and has reference structure visible in MR images. Combined with a specially designed algorithm, the imaging plane can be aligned to a predefined coordinate system in one step, using a single slice through the device. The device can be produced at low cost and is suitable for routine examinations as well as surgical planning.
RV Mulkern, JL Bowers, A Heff, CR Guttmann, and RH Sadowski. 1996. “Triexponential decomposition of 1H spin-lattice relaxation decay curves of paramagnetically doped red cell suspensions at 7 T.” Phys Med Biol, 41, 2, Pp. 255-68.Abstract
The spin-lattice relaxation behaviour of protons in paramagnetically doped red cell suspensions at two haematocrit levels has been studied using high-field (7 T) inversion recovery data. The resulting relaxation decay curves were found to be best characterized by triexponential functions. The two-site exchange model, generally applied to biexponential relaxation data in calculating red cell water exchange parameters, was applied to the two fastest-relaxing fractions of the triexponential fits. The intracellular to extracellular water exchange rates so obtained were in good agreement with literature values. Additional exchange parameters including intracellular and extracellular water volume fractions and extracellular relaxation rates were also calculated directly from the relaxation data and found to be consistent with sample haematocrits and with independent relaxation rate measurements of the resuspension medium. The small-amplitude, slowly relaxing third component recovered from the triexponential fits of the relaxation data is attributed to intracellular haemoglobin protons.
1995
S Warfield, J Dengler, J Zaers, CR Guttmann, WM Wells, GJ Ettinger, J Hiller, and R Kikinis. 1995. “Automatic identification of gray matter structures from MRI to improve the segmentation of white matter lesions.” J Image Guid Surg, 1, 6, Pp. 326-38.Abstract
The segmentation of MRI scans of patients with white matter lesions (WML) is difficult because the MRI characteristics of WML are similar to those of gray matter. Intensity-based statistical classification techniques misclassify some WML as gray matter and some gray matter as WML. We developed a fast elastic matching algorithm that warps a reference data set containing information about the location of the gray matter into the approximate shape of the patient's brain. The region of white matter was segmented after segmenting the cortex and deep gray matter structures. The cortex was identified by using a three-dimensional, region-growing algorithm that was constrained by anatomical, intensity gradient, and tissue class parameters. White matter and WML were then segmented without interference from gray matter by using a two-class minimum-distance classifier. Analysis of double-echo spin-echo MRI scans of 16 patients with clinically determined multiple sclerosis (MS) was carried out. The segmentation of the cortex and deep gray matter structures provided anatomical context. This was found to improve the segmentation of MS lesions by allowing correct classification of the white matter region despite the overlapping tissue class distributions of gray matter and MS lesion.
CR Guttmann, SS Ahn, L Hsu, R Kikinis, and FA Jolesz. 1995. “The evolution of multiple sclerosis lesions on serial MR.” AJNR Am J Neuroradiol, 16, 7, Pp. 1481-91.Abstract
PURPOSE: To characterize temporal changes in signal intensity patterns of multiple sclerosis lesions on serial MR. METHODS: T1-, T2-, proton density-, and contrast-enhanced T1-weighted MR was performed on five patients with relapsing-remitting multiple sclerosis at least 22 times in the course of 1 year. RESULTS: Forty-three enhancing lesions and 1 new lesion that never showed enhancement were detected and followed for periods ranging from approximately 4 weeks to 1 year (total of 702 time points). At first detection the center of new lesions was brighter than the periphery (20 of 24 new lesions on proton density-weighted and 19 of 23 new lesions on contrast-enhanced images). On contrast-enhanced images, ring hyperintensity was predominant at time points later than 29 days. As lesions aged, a residual rim of "nonenhancing" hyperintensity often was noted on contrast-enhanced images. Some older lesions (> 1 year) showed similar appearance on unenhanced T1-weighted images. On proton density-weighted images ring hyperintensity was most frequent 2 to 4 months after lesion detection. The estimated average duration of gadopentetate dimeglumine enhancement was 1 to 2 months. CONCLUSIONS: A lesion evolution pattern relevant to MR was inferred. We believe that specific information about the histopathologic evolution of a lesion may be extracted not only from contrast-enhanced but also from nonenhanced serial MR. Assessment of drugs targeting specific phases of lesion evolution could benefit from quantitative pattern analysis of routine MR images.
LJ Kleine, RV Mulkern, CR Guttmann, VM Colucci, and FA Jolesz. 1995. “In vivo characterization of cytotoxic intracellular edema by multicomponent analysis of transverse magnetization decay curves.” Acad Radiol, 2, 5, Pp. 365-72.Abstract
RATIONALE AND OBJECTIVES: We investigated the multicompartmental nature of T2 decay in a specific white matter edema model. METHODS: Triethyltin (TET) intoxication was produced in six male New Zealand White rabbits. Images were obtained over the 23-day study duration using a 64-echo Carr-Purcell-Meiboom-Gill (CPMG) sequence (repetition time = 3000 msec, echo time = 20 msec). T2 decay curves were extracted from 0.7 x 0.7 x 3.0 mm3 voxels in the corpus callosum and contiguous white matter tracts, cortex, thalamic nuclei, hypothalamic nuclei, and the masseter muscles. The curves were fit with biexponential functions. RESULTS: Increased signal intensity in the corpus callosum was evident 2-3 days after the first TET injection. At this time, a substantial slowly relaxing component appeared in the decay curves of the corpus callosum and, to a lesser extent, in the thalamus and hypothalamus. Changes in the rabbits' body weight, general physical condition, and neurologic state paralleled the growth and regression of the second, slowly relaxing component. CONCLUSION: The appearance and regression of a slowly decaying second component in the T2 decay curve is consistent with the formation and shrink-age of intracellular vesicles in the intramyelin sheaths of central white matter.
RV Mulkern, J Meng, K Oshio, DS Williamson, HS Lilly, CR Guttmann, and D Jaramillo. 1995. “Spectroscopic imaging of the knee with line scan CPMG sequences.” J Comput Assist Tomogr, 19, 2, Pp. 247-55.Abstract
OBJECTIVE: A line scan spectroscopic imaging method providing variable T2-weighted spectra from many small voxels along selected tissue columns was applied to study the chemical composition of hematopoietic and fatty marrow in the knees of adults and children. MATERIALS AND METHODS: Line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequences were implemented on a 1.5 T clinical scanner. Variable T2-weighted proton spectra from 128 locations along 20 cm long, 5 mm2 columns oriented superiorly to inferiorly through knees were collected from eight healthy adults and eight children. RESULTS: In adult yellow marrow, olefinic protons, water, a composite lipid proton peak, and methyl/methylene protons contributed 6.4 +/- 0.4, 4.2 +/- 1.5, 7.2 +/- 0.5, and 82.2 +/- 1.9% (mean +/- SD) to the spectra, respectively. Marrow spectra were largely independent of position along the column. Marrow spectra of normal children showed distinct positional dependences. Epiphyseal marrow spectra of children (8-16 years old) resembled adult spectra but with more water (mean 15 vs. 4%). Metaphyseal marrow had higher, variable water content, reflecting the extent of marrow conversion and generally obscuring the olefinic proton peak. CONCLUSIONS: Spectroscopic imaging of columns is a time-efficient method for sampling extensive regions of bone marrow with high spatial resolution. It should prove useful for proton spectroscopic studies of hematologic pathologies and conditions requiring the monitoring of lipid composition.
1994
RV Mulkern, J Meng, K Oshio, CR Guttmann, and D Jaramillo. 1994. “Bone marrow characterization in the lumbar spine with inner volume spectroscopic CPMG imaging studies.” J Magn Reson Imaging, 4, 4, Pp. 585-9.Abstract
The authors describe new magnetic resonance (MR) spectroscopic and postprocessing methods for characterizing major proton peaks and their spectral T2 values in many small voxels throughout extensive regions of bone marrow within the adult lumbar spine. The techniques are based on spectroscopic interrogation of 128 voxels along columns oriented through the spine at eight TE values. Mean fat content measurements, based on quantification of the proton peaks of water and saturated fat (-CH2-)n, corrected for T2 decay, ranged from 40% to 60%. The mean T2 value of the lipid peak, 113 msec +/- 21, was significantly longer (P < .001) than that of water (71 msec +/- 14). The techniques combine features of MR spectroscopy and imaging most suited for spatially efficient coverage of bone marrow at spectral resolutions sufficient for intra-voxel fat or water content measurements. The methods introduced provide a practical, quantitative means for characterizing vertebral marrow in diseases affecting marrow cellularity.
SJ Khoury, CR Guttmann, EJ Orav, MJ Hohol, SS Ahn, L Hsu, R Kikinis, GA Mackin, FA Jolesz, and HL Weiner. 1994. “Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden.” Neurology, 44, 11, Pp. 2120-4.Abstract
We followed 18 multiple sclerosis patients clinically and with repeated brain MRIs with and without gadolinium for over 1 year. Clinical evaluations included scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI) scale. There was a significant correlation between the change in EDSS or AI and the change in number of lesions on MRI and between cumulative number of lesions on MRI and cumulative change in EDSS or AI. Our findings support the validity of MRI as a measure of clinical activity and potentially as an objective quantitative outcome measure for assessing response to therapy.
1993
A el-Ouahabi, CR Guttmann, SG Hushek, AR Bleier, K Dashner, P Dikkes, PM Black, and FA Jolesz. 1993. “MRI guided interstitial laser therapy in a rat malignant glioma model.” Lasers Surg Med, 13, 5, Pp. 503-10.Abstract
We have used MR monitoring to guide and evaluate the effects of the Nd:YAG interstitial laser on a well-characterized rat brain tumor model (C6). MRI was used to determine the tumor size, verify the location of the interstitial probe, and evaluate the size and location of the laser-induced lesion during and after treatment. During laser irradiation, an irreversible loss of signal intensity at the fiber tip and a reversible decrease in signal intensity around it were observed with MRI. None of the treatment protocols affected mean rat survival significantly. Although MRI-guided interstitial laser therapy appears to be safe and easy, it does not provide a curative treatment for spatially disseminated gliomas where a "target volume" cannot be adequately defined. Better results can be expected, especially in well-defined tumors, with improvements of both the imaging techniques and the laser treatment protocol.
1992
R Kikinis, ME Shenton, G Gerig, J Martin, M Anderson, D, D Metcalf, CR Guttmann, RW McCarley, W Lorensen, and H Cline. 1992. “Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging.” J Magn Reson Imaging, 2, 6, Pp. 619-29.Abstract
A computerized system for processing spin-echo magnetic resonance (MR) imaging data was implemented to estimate whole brain (gray and white matter) and cerebrospinal fluid volumes and to display three-dimensional surface reconstructions of specified tissue classes. The techniques were evaluated by assessing the radiometric variability of MR volume data and by comparing automated and manual procedures for measuring tissue volumes. Results showed (a) the homogeneity of the MR data and (b) that automated techniques were consistently superior to manual techniques. Both techniques, however, were affected by the complexity of the structure, with simpler structures (eg, the intracranial cavity) showing less variability and better spatial correlation of segmentation results between raters. Moreover, the automated techniques were completed for whole brain in a fraction of the time required to complete the equivalent segmentation manually. Additional evaluations included interrater reliability and an evaluation that included longitudinal measurement, in which one subject was imaged sequentially 24 times, with reliability computed from data collected by three raters over 1 year. Results showed good reliability for the automated segmentation procedures.

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