26 results on '"Tkach J"'
Search Results
2. Periictal Diffusion-Weighted Imaging in a Case of Lesional Epilepsy
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Diehl, B., Najm, I., Ruggieri, P., Foldvary, N., Mohamed, A., Tkach, J., Morris, H., Barnett, G., Fisher, E., Duda, J., and Lüders, H. O.
- Published
- 1999
3. White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposue
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Merhar, S.L., primary, Parikh, N.A., additional, Braimah, A., additional, Poindexter, B.B., additional, Tkach, J., additional, and Kline-Fath, B., additional
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- 2019
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4. Gelled versus nongelled phantom material for measurement of MRI-induced temperature increases with bioimplants
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Park, S.M., Nyenhuis, J.A., Smith, C.D., Lim, E.J., Foster, K.S., Baker, K.B., Hrdlicka, G., Rezai, A.R., Ruggieri, P., Sharan, A., Shellock, F.G., Stypulkowski, P.H., and Tkach, J.
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Magnetic resonance imaging -- Research ,Brain -- Research ,Business ,Electronics ,Electronics and electrical industries - Abstract
Measurements in phantoms are used to predict temperature changes that would occur in vivo for medical implants due to the radio frequency (RF) field in magnetic resonance imaging (MRI). In this study, the impact of concentration of the gelling agent in a saline-based phantom on the RF-induced temperature rise was measured using an apparatus that accurately reproduces the RF environment present in a 1.5-T whole-body MR system. The temperature was measured using fluoroptic thermometry at the electrode and other sites for a deep brain neurostimulation system. The average power deposition in the 30-kg phantom was about 1.5 W/kg. Four phantom formulations were evaluated, using different concentrations of polyacrylic acid (PAA) added to saline solution, with NaCl concentration adjusted to maintain an electrical conductivity near 0.24 S/m. The greatest temperature rises occurred at the electrode, ranging from 16.2 [degrees]C for greatest concentration of PAA to 2.9 [degrees]C for only saline solution. The temperature rise attained the maximal value for sufficient concentration of PAA. Similar behavior was observed in the temperature versus time relationship near a current-carrying resistor, immersed in gel and saline, which was used to model a localized heat source. The temperature rise for insufficient PAA concentration is reduced due to convection of phantom material. In conclusion, an appropriate gelling agent is required to accurately simulate the thermal properties of body tissues for measurements of RF-induced heating with medical implants. Index Terms--Deep brain stimulation, heating, magnetic resonance imaging (MRI), medical implant, radio frequency.
- Published
- 2003
5. Lumbar degenerative disk disease: prospective comparison of conventional T2-weighted spin-echo imaging and T2-weighted rapid acquisition relaxation-enhanced imaging
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Ross, J S, Ruggieri, P, Tkach, J, Obuchowski, N, Dillinger, J, Masaryk, T J, and Modic, M T
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Spinal Stenosis ,Humans ,Comparative Study ,Spinal Diseases ,Prospective Studies ,Spondylolisthesis ,Artifacts ,Intervertebral Disc ,Magnetic Resonance Imaging ,Intervertebral Disc Displacement - Abstract
PURPOSE: To compare conventional T2-weighted spin-echo imaging with a rapid acquisition relaxation enhanced (RARE) technique in the routine evaluation of lumbar degenerative disk disease. METHODS: Thirty consecutive patients referred for evaluation of the lumbar spine for suspected degenerative disk disease were evaluated with sagittal and axial T1-weighted spin-echo, conventional T2-weighted spin-echo, and T2-weighted RARE "turbo spin-echo" sequences (4000/93/2 (repetition time/echo time/excitations), 192 x 256, echo train length of 8). Conventional T2-weighted and RARE images were evaluated independently by two neuroradiologists for image quality, presence of artifacts, cerebrospinal fluid signal intensity, extradural interface conspicuity, intradural nerve root conspicuity, soft-tissue detail, and signal intensity of normal and degenerated intervertebral disks. RESULTS: Both readers rated the cerebrospinal fluid signal higher, the extradural interface conspicuity higher, and the nerve root detail greater on the turbo spin-echo than on conventional spin-echo images. Neither reader had a significant difference in ranking "normal" or "degenerated" disk signal on the two sequences. Both readers rated soft-tissue detail higher for conventional than for turbo spin-echo. CONCLUSION: RARE sequences can replace conventional T2-weighted spin-echo sagittal studies for degenerative lumbar disk disease.
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- 1993
6. The value of fast gradient-echo MR sequences in the evaluation of brain disease
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Steinberg, P M, Ross, J S, Modic, M T, Tkach, J, Masaryk, T J, and Haacke, E M
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Brain Diseases ,Brain Neoplasms ,Journal Article ,Humans ,Magnetic Resonance Imaging - Abstract
One-hundred-fifteen patients thought to have intracranial disease were studied with various two-dimensional short repetition time, partial-flip-angle gradient-echo techniques: at 1.0 T, fast low-angle short (FLASH) at 10 degrees and 30 degrees and fast imaging with steady-state precession (FISP) at 60 degrees; at 1.5 T, FLASH 10 degrees, 30 degrees, and 60 degrees, FISP 60 degrees, and contrast-enhanced fast steady state at 60 degrees. These sequences were compared with a T2-weighted spin-echo sequence to determine the relative sensitivities of these techniques in detecting parenchymal lesions. Except for hemorrhagic lesions a substantial number of abnormalities were either not visible or poorly seen on the partial-flip-angle gradient-echo sequences. Minimizing echo time (6-9 msec) to decrease magnetic susceptibility effects did not improve lesion detection. Current usage of two-dimensional gradient-echo techniques for lesion detection is limited, except when calcification or hemorrhage is involved. Their utility may be expanded via the incorporation of three-dimensional techniques and IV contrast agents.
- Published
- 1990
7. Reduction in neural activation to high-calorie food cues in obese endometrial cancer survivors after a behavioral lifestyle intervention: a pilot study
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Nock Nora L, Dimitropolous Anastasia, Tkach Jean, Frasure Heidi, and vonGruenigen Vivan
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Obesity ,Endometrial cancer ,fMRI ,Reward ,High-calorie foods ,Lifestyle intervention ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract Background Obesity increases the risk of endometrial cancer (EC) and obese EC patients have the highest risk of death among all obesity-associated cancers. However, only two lifestyle interventions targeting this high-risk population have been conducted. In one trial, food disinhibition, as determined by the Three-Factor Eating Questionnaire, decreased post-intervention compared to baseline, suggesting an increase in emotional eating and, potentially, an increase in food related reward. Therefore, we evaluated appetitive behavior using functional magnetic resonance imaging (fMRI) and a visual food task in 8 obese, Stage I/II EC patients before and after a lifestyle intervention (Survivors in Uterine Cancer Empowered by Exercise and a Healthy Diet, SUCCEED), which aimed to improve nutritional and exercise behaviors over 16 group sessions in 6 months using social cognitive theory. Results Congruent to findings in the general obese population, we found that obese EC patients, at baseline, had increased activation in response to high- vs. low-calorie food cues after eating a meal in brain regions associated with food reward (insula, cingulate gyrus; precentral gyrus; whole brain cluster corrected, p Conclusions Our preliminary results suggest behavioral lifestyle interventions may help to reduce high-calorie food reward in obese EC survivors who are at a high-risk of death. To our knowledge, this is the first study to demonstrate such changes.
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- 2012
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8. Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.
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Dean DC 3rd, Tisdall MD, Wisnowski JL, Feczko E, Gagoski B, Alexander AL, Edden RAE, Gao W, Hendrickson TJ, Howell BR, Huang H, Humphreys KL, Riggins T, Sylvester CM, Weldon KB, Yacoub E, Ahtam B, Beck N, Banerjee S, Boroday S, Caprihan A, Caron B, Carpenter S, Chang Y, Chung AW, Cieslak M, Clarke WT, Dale A, Das S, Davies-Jenkins CW, Dufford AJ, Evans AC, Fesselier L, Ganji SK, Gilbert G, Graham AM, Gudmundson AT, Macgregor-Hannah M, Harms MP, Hilbert T, Hui SCN, Irfanoglu MO, Kecskemeti S, Kober T, Kuperman JM, Lamichhane B, Landman BA, Lecour-Bourcher X, Lee EG, Li X, MacIntyre L, Madjar C, Manhard MK, Mayer AR, Mehta K, Moore LA, Murali-Manohar S, Navarro C, Nebel MB, Newman SD, Newton AT, Noeske R, Norton ES, Oeltzschner G, Ongaro-Carcy R, Ou X, Ouyang M, Parrish TB, Pekar JJ, Pengo T, Pierpaoli C, Poldrack RA, Rajagopalan V, Rettmann DW, Rioux P, Rosenberg JT, Salo T, Satterthwaite TD, Scott LS, Shin E, Simegn G, Simmons WK, Song Y, Tikalsky BJ, Tkach J, van Zijl PCM, Vannest J, Versluis M, Zhao Y, Zöllner HJ, Fair DA, Smyser CD, and Elison JT
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- Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Longitudinal Studies, Magnetic Resonance Spectroscopy methods, Neuroimaging methods, Prospective Studies, Multicenter Studies as Topic, Brain diagnostic imaging, Brain growth & development, Child Development physiology, Magnetic Resonance Imaging methods
- Abstract
The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Tobias Kober and Tom Hilbert are employees of Siemens Healthineers International AG, Switzerland. Yulin Chang is an employee of Siemens Medical Solutions USA Inc. Dan Rettmann and Ralph Noeske are employed by GE HealthCare. Guillaume Gilbert, Yansong Zhao, Sandeep Ganji, and Maarten Versluis are employed by Philips Healthcare. Carina Lucena, Lucky Heisler-Roman, and Dhruman Goradia are employed by PrimeNeuro Inc. Under a license agreement between Philips and the Johns Hopkins University, Dr. van Zijl and the University are entitled to fees related to an imaging device used in the study discussed for publication. Dr. van Zijl also is a paid lecturer for Philips and receives research support from Philips. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Damien Fair is a patent holder on the Framwise Integrated Real-Time Motion Monitoring (FIRMM) software. He is also a co-founder of Turing Medical Technologies, Inc. The nature of this financial interest and the design of the study have been reviewed by two committees at the University of Minnesota. They have put in place a plan to help ensure that this research is not affected by the financial interest. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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9. Structural connectivity at term equivalent age and language in preterm children at 2 years corrected.
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Barnes-Davis ME, Williamson BJ, Kline JE, Kline-Fath BM, Tkach J, He L, Yuan W, and Parikh NA
- Abstract
We previously reported interhemispheric structural hyperconnectivity bypassing the corpus callosum in children born extremely preterm (<28 weeks) versus term children. This increased connectivity was positively associated with language performance at 4-6 years of age in our prior work. In the present study, we aim to investigate whether this extracallosal connectivity develops in extremely preterm infants at term equivalent age by leveraging a prospective cohort study of 350 very and extremely preterm infants followed longitudinally in the Cincinnati Infant Neurodevelopment Early Prediction Study. For this secondary analysis, we included only children born extremely preterm and without significant brain injury ( n = 95). We use higher-order diffusion modelling to assess the degree to which extracallosal pathways are present in extremely preterm infants and predictive of later language scores at 22-26 months corrected age. We compare results obtained from two higher-order diffusion models: generalized q-sampling imaging and constrained spherical deconvolution. Advanced MRI was obtained at term equivalent age (39-44 weeks post-menstrual age). For structural connectometry analysis, we assessed the level of correlation between white matter connectivity at the whole-brain level at term equivalent age and language scores at 2 years corrected age, controlling for post-menstrual age, sex, brain abnormality score and social risk. For our constrained spherical deconvolution analyses, we performed connectivity-based fixel enhancement, using probabilistic tractography to inform statistical testing of the hypothesis that fibre metrics at term equivalent age relate to language scores at 2 years corrected age after adjusting for covariates. Ninety-five infants were extremely preterm with no significant brain injury. Of these, 53 had complete neurodevelopmental and imaging data sets that passed quality control. In the connectometry analyses adjusted for covariates and multiple comparisons ( P < 0.05), the following tracks were inversely correlated with language: bilateral cerebellar white matter and middle cerebellar peduncles, bilateral corticospinal tracks, posterior commissure and the posterior inferior fronto-occipital fasciculus. No tracks from the constrained spherical deconvolution/connectivity-based fixel enhancement analyses remained significant after correction for multiple comparisons. Our findings provide critical information about the ontogeny of structural brain networks supporting language in extremely preterm children. Greater connectivity in more posterior tracks that include the cerebellum and connections to the regions of the temporal lobes at term equivalent age appears to be disadvantageous for language development., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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10. Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology.
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Kline JE, Dudley J, Illapani VSP, Li H, Kline-Fath B, Tkach J, He L, Yuan W, and Parikh NA
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- Infant, Newborn, Infant, Humans, Infant, Premature, Magnetic Resonance Imaging, Brain anatomy & histology, Diffusion Tensor Imaging methods, White Matter diagnostic imaging, White Matter pathology
- Abstract
Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models - Constrained Spherical Deconvolution (CSD) and neurite orientation dispersion and density index (NODDI) - to better characterize the macro and microstructural properties of DWMA and inform the ongoing debate around the clinical significance of DWMA. With increasing DWMA volume, fiber density broadly decreased throughout the white matter and fiber cross-section decreased in the major sensorimotor tracts. Neurite orientation dispersion decreased in the centrum semiovale, corona radiata, and temporal lobe. These findings provide insight into DWMA's biological underpinnings and demonstrate that it is a serious pathology., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2022
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11. Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants.
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Chandwani R, Kline JE, Harpster K, Tkach J, and Parikh NA
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- Diffusion Tensor Imaging, Female, Humans, Infant, Infant, Extremely Premature, Infant, Newborn, Male, Neural Pathways diagnostic imaging, Neural Pathways pathology, Prospective Studies, Risk, Sensorimotor Cortex diagnostic imaging, Sensorimotor Cortex pathology, Cerebral Palsy diagnostic imaging, Cerebral Palsy pathology, White Matter diagnostic imaging, White Matter pathology
- Abstract
Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
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- 2021
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12. Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.
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Wisnowski JL, Bluml S, Panigrahy A, Mathur AM, Berman J, Chen PK, Dix J, Flynn T, Fricke S, Friedman SD, Head HW, Ho CY, Kline-Fath B, Oveson M, Patterson R, Pruthi S, Rollins N, Ramos YM, Rampton J, Rusin J, Shaw DW, Smith M, Tkach J, Vasanawala S, Vossough A, Whitehead MT, Xu D, Yeom K, Comstock B, Heagerty PJ, Juul SE, Wu YW, and McKinstry RC
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- Asphyxia, Biomarkers, Clinical Trial Protocols as Topic, Humans, Infant, Newborn, Multicenter Studies as Topic, Neuroimaging, Erythropoietin, Hypoxia-Ischemia, Brain diagnostic imaging, Hypoxia-Ischemia, Brain drug therapy
- Abstract
Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms., Methods and Analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans., Ethics and Dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor., Trial Registration Number: NCT02811263; Pre-result., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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13. Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.
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Ooi MB, Li Z, Robison RK, Wang D, Anderson AG 3rd, Zwart NR, Bakhru A, Nagaraj S, Mathews T, Hey S, Koonen JJ, Dimitrov IE, Friel HT, Lu Q, Obara M, Saha I, Wang H, Wang Y, Zhao Y, Temkit M, Hu HH, Chenevert TL, Togao O, Tkach JA, Nagaraj UD, Pinho MC, Gupta RK, Small JE, Kunst MM, Karis JP, Andre JB, Miller JH, Pinter NK, and Pipe JG
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- Adult, Aged, Artifacts, Female, Humans, Image Enhancement methods, Male, Middle Aged, Brain diagnostic imaging, Magnetic Resonance Imaging methods, Neuroimaging methods
- Abstract
Background and Purpose: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit., Materials and Methods: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences., Results: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility ( P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively ( P < .05)., Conclusions: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation., (© 2020 by American Journal of Neuroradiology.)
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- 2020
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14. White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposure.
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Merhar SL, Parikh NA, Braimah A, Poindexter BB, Tkach J, and Kline-Fath B
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- Female, Humans, Infant, Infant, Newborn, Longitudinal Studies, Magnetic Resonance Imaging methods, Male, Neuroimaging methods, Pregnancy, Analgesics, Opioid adverse effects, Brain drug effects, Brain pathology, Prenatal Exposure Delayed Effects pathology, White Matter drug effects, White Matter pathology
- Abstract
Previous studies have not found structural injury or brain malformations in infants and children with prenatal opioid exposure. As part of an ongoing study evaluating neuroimaging in infants with prenatal opioid exposure, we reviewed structural brain MR imaging in 20 term infants with prenatal opioid exposure and 20 term controls at 4-8 weeks of age. We found that 8 of the 20 opioid-exposed infants had punctate white matter lesions or white matter signal abnormality on structural MR imaging, and 2 of the opioid-exposed infants had a septopreoptic fusion anomaly. No controls had white matter injury or structural malformations. Our findings underscore the importance of clinical neurodevelopmental follow-up and the need for more comprehensive imaging and long-term outcomes research following prenatal opioid exposure., (© 2019 by American Journal of Neuroradiology.)
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- 2019
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15. SET8 methyltransferase activity during the DNA double-strand break response is required for recruitment of 53BP1.
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Dulev S, Tkach J, Lin S, and Batada NN
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- Cell Line, Tumor, HEK293 Cells, Histone Deacetylases metabolism, Histone-Lysine N-Methyltransferase genetics, Histones metabolism, Humans, Intracellular Signaling Peptides and Proteins genetics, Protein Binding, Protein Transport, Tumor Suppressor p53-Binding Protein 1, DNA Breaks, Double-Stranded, DNA End-Joining Repair, Histone-Lysine N-Methyltransferase metabolism, Intracellular Signaling Peptides and Proteins metabolism
- Abstract
DNA double-strand breaks (DSBs) activate a signaling pathway known as the DNA damage response (DDR) which via protein-protein interactions and post-translational modifications recruit signaling proteins, such as 53BP1, to chromatin flanking the lesion. Depletion of the SET8 methyltransferase prevents accumulation of 53BP1 at DSBs; however, this phenotype has been attributed to the role of SET8 in generating H4K20 methylation across the genome, which is required for 53BP1 binding to chromatin, prior to DNA damage. Here, we report that SET8 acts directly at DSBs during the DNA damage response (DDR). SET8 accumulates at DSBs and is enzymatically active at DSBs. Depletion of SET8 just prior to the induction of DNA damage abrogates 53BP1's accumulation at DSBs, suggesting that SET8 acts during DDR. SET8's occupancy at DSBs is regulated by histone deacetylases (HDACs). Finally, SET8 is functionally required for efficient repair of DSBs specifically via the non-homologous end-joining pathway (NHEJ). Our findings reveal that SET8's active role during DDR at DSBs is required for 53BP1's accumulation., (© 2014 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
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- 2014
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16. Cortical stimulation for language mapping in focal epilepsy: correlations with tractography of the arcuate fasciculus.
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Diehl B, Piao Z, Tkach J, Busch RM, LaPresto E, Najm I, Bingaman B, Duncan J, and Lüders H
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- Electrodes, Implanted, Humans, Organ Size physiology, Reference Values, Tomography, X-Ray Computed, Brain Mapping methods, Diffusion Tensor Imaging methods, Electroencephalography, Epilepsies, Partial physiopathology, Frontal Lobe physiopathology, Image Processing, Computer-Assisted methods, Imaging, Three-Dimensional methods, Language, Magnetic Resonance Imaging methods, Nerve Net physiopathology, Signal Processing, Computer-Assisted, Temporal Lobe physiopathology
- Abstract
Purpose: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (fractional anisotropy, FA) of water diffusion and allows visualization of major white matter tracts. The arcuate fasciculus (AF) connects anterior (Broca's) and posterior (Wernicke's) language areas. We hypothesized that essential language areas identified by direct cortical stimulation would colocalize with areas revealing subcortical connectivity via the AF., Methods: Fourteen patients with pharmacoresistant left hemispheric epilepsy and left hemisphere language dominance underwent invasive evaluations for localization of epileptogenicity and functional mapping. DTI and T1-weighted volumetric magnetic resonance imaging (MRI) scans were coregistered, and subdural grid electrodes identified on postimplantation computed tomography (CT) scans were also coregistered to the MRI scans. The AF was reconstructed from a region lateral to the corona radiata on the FA map. Colocalization, defined as <1 cm between the AF and the electrode positions delineating language cortex, was visually assessed with excellent reliability (Cronbach's alpha = 0.98)., Results: A total of 71 subdural grid contacts were overlying language cortex. Nineteen contacts in eight patients were over Broca's area, 16 of which (84.2%) colocalized with the AF. Fifty-two contacts in 10 patients were over Wernicke's area, with colocalization in 29 patients (55.8%). Colocalization was significantly greater in anterior regions than in posterior regions [chi(2)(1) = 4.850, p < 0.05]., Discussion: The AF, as visualized with DTI, colocalized well with anterior language areas, but less so with posterior language areas, inferring that the latter are more spatially dispersed.
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- 2010
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17. Abnormalities in diffusion tensor imaging of the uncinate fasciculus relate to reduced memory in temporal lobe epilepsy.
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Diehl B, Busch RM, Duncan JS, Piao Z, Tkach J, and Lüders HO
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- Adult, Anisotropy, Epilepsy, Temporal Lobe complications, Female, Functional Laterality physiology, Hippocampus pathology, Humans, Male, Memory Disorders diagnosis, Memory Disorders etiology, Middle Aged, Neuropsychological Tests, Sclerosis pathology, Diffusion Magnetic Resonance Imaging, Epilepsy, Temporal Lobe pathology, Temporal Lobe anatomy & histology
- Abstract
Aims: To use Diffusion Tensor Imaging (DTI) to explore structural integrity and connectivity of the uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) and its relationship to memory performance., Methods: DTI and UF reconstruction were performed in 28 patients with TLE (18 left, 10 right) and 10 normal controls. Differences between left and right UF fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and correlations between DTI measures and memory scores in the TLE groups were computed., Results: In controls, FA was higher in the left than right UF (p < 0.01). In left TLE, FA values were lower and ADC values higher than controls in the left UF and ADC values were higher in the right UF (all p < 0.05). In right TLE, ADCs were higher in the left and right UF compared to controls, and FA was reduced in the left UF (all p < 0.05). In left TLE, ADCs in the left UF were negatively correlated with Auditory Immediate (p < 0.05) and Delayed Memory (p < 0.01). Visual Delayed Memory was positively correlated with reduced FA in the ROI of the right UF and increased radial diffusivities (p < 0.05). No significant correlations were found in right TLE. Thus, DTI values correlated with memory scores in the expected direction in patients with left TLE., Conclusions: Abnormal diffusion measures in the UF ipsilateral to the epileptogenic zone suggest that integrity of the UF is related to memory performance in patients with left TLE. Larger sample sizes are needed to evaluate structure-function correlations further.
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- 2008
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18. The mind's eye: functional MR imaging evaluation of golf motor imagery.
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Ross JS, Tkach J, Ruggieri PM, Lieber M, and Lapresto E
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- Adult, Brain Mapping, Frontal Lobe physiology, Humans, Male, Middle Aged, Motor Cortex physiology, Motor Skills physiology, Parietal Lobe physiology, Practice, Psychological, Cerebellum physiology, Cerebral Cortex physiology, Golf physiology, Image Processing, Computer-Assisted, Imagination physiology, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Psychomotor Performance physiology
- Abstract
Background and Purpose: Mental imagery involves rehearsing or practicing a task in the mind with no physical movement. The technique is commonly used, but the actual physical foundation of imagery has not been evaluated for the fast, complex, automatic motor movement of the golf swing. This study evaluated motor imagery of the golf swing, of golfers of various handicaps, by using functional MR imaging to assess whether areas of brain activation could be defined by this technique and to define any association between activated brain areas and golf skill., Methods: Six golfers of various handicap levels were evaluated with functional MR imaging during a control condition and during mental imagery of their golf swing. Two control conditions were evaluated--"rest" and "wall"--and were then subtracted from the experimental condition to give the functional activation map. These control conditions were then tested against the golf imagery; the participants were told to mentally rehearse their golf swings from a first person perspective. The percentages of activated pixels in 137 defined regions of interest were calculated., Results: The "rest-versus-golf" paradigm showed activation in motor cortex, parietal cortex, frontal lobe, cerebellum, vermis, and action planning areas (frontal and parietal cortices, supplementary motor area, cerebellum) and areas involved with error detection (cerebellum). Vermis, supplementary motor area, cerebellum, and motor regions generally showed the greatest activation. Little activation was seen in the cingulate gyrus, right temporal lobe, deep gray matter, and brain stem. A correlation existed between increased number of areas of activation and increased handicap., Conclusion: This study showed the feasibility of defining areas of brain activation during imagery of a complex, coordinated motor task. Decreased brain activation occurred with increased golf skill level for the supplementary motor area and cerebellum with little activation of basal ganglia.
- Published
- 2003
19. Postictal diffusion-weighted imaging for the localization of focal epileptic areas in temporal lobe epilepsy.
- Author
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Diehl B, Najm I, Ruggieri P, Tkach J, Mohamed A, Morris H, Wyllie E, Fisher E, Duda J, Lieber M, Bingaman W, and Lüders HO
- Subjects
- Adolescent, Adult, Diffusion, Electroencephalography statistics & numerical data, Epilepsy, Temporal Lobe metabolism, Epilepsy, Temporal Lobe physiopathology, Female, Hippocampus metabolism, Hippocampus pathology, Humans, Male, Middle Aged, Sclerosis metabolism, Temporal Lobe metabolism, Body Water metabolism, Brain metabolism, Epilepsy, Temporal Lobe diagnosis, Magnetic Resonance Imaging methods, Temporal Lobe physiopathology
- Abstract
Purpose: Diffusion-weighted MR imaging (DWI) is a novel technique to delineate focal areas of cytotoxic edema of various etiologies. We hypothesized that DWI may also detect the epileptogenic region and adjacent areas during the ictal and early postictal periods in patients with temporal lobe epilepsy (TLE)., Methods: We studied patients with intractable TLE (n = 9), due to hippocampal sclerosis (HS, n = 7), left mesial temporal lobe tumor (n = 1), and of unknown etiology (n = 1). Informed consent was obtained before inclusion in the study. All patients with single short seizures were scanned immediately after EEG-documented seizures (between 45 and 150 min); one of two patients in status was scanned 14 h after cessation of seizures. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps., Results: We found significant decreases in ADC postictally in one of six patients with TLE due to HS and single short seizures. One patient with an incompletely resected temporal lobe tumor also exhibited ADC abnormalities. One patient in focal status epilepticus revealed a decrease in ADC, and one patient with a continuous aura had no DWI abnormality., Conclusions: Postictal DWI technique may occasionally help delineate epileptic areas in some patients with TLE. Yield is low in patients with HS and single short seizures: it may be higher in patients with tumor or status epilepticus.
- Published
- 2001
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20. Hemorrhage detected using MR imaging in the setting of acute stroke: an in vivo model.
- Author
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Perl J 2nd, Tkach JA, Porras-Jimenez M, Lieber M, Obuchowski N, Ross JS, Ding XP, Ruggieri PM, Shearer DM, Khajavi K, and Masaryk TJ
- Subjects
- Acute Disease, Animals, Brain pathology, Disease Models, Animal, Dogs, ROC Curve, Sensitivity and Specificity, Cerebral Hemorrhage diagnosis, Image Enhancement, Magnetic Resonance Imaging, Subarachnoid Hemorrhage diagnosis
- Abstract
Background and Purpose: The treatment algorithm for acute cerebrovascular accidents has traditionally sorted these accidents as either hemorrhagic or nonhemorrhagic, and MR imaging, with its ability to allow expeditious assessment of vascular substrates and regional blood volume, is well suited for this purpose. Our purpose was to delineate the accuracy of MR imaging in acute, hemorrhagic forms of stroke during the time frame considered beneficial for intervention in an animal model., Methods: Eighteen dogs with small, iatrogenic parenchymal, subarachnoid hemorrhage (SAH), or both were serially scanned over the initial 6-hour postictal period. Confirmatory pathologic specimens and 3-hour postictal CT scans were obtained in all animals. The MR and CT studies were then interpreted in a blinded fashion by two neuroradiologists for the presence of hemorrhage. The results were subjected to receiver operating characteristic analysis., Results: MR imaging depicted acute parenchymal hemorrhage and SAH with a high degree of accuracy at 1.5 T. This finding was independent of each of the time points studied during the 6-hour window. For SAH, the MR accuracy for reader 1 was 0.86 (95% CI, 0.76-0.97); for reader 2, accuracy was 0.85 (95% CI, 0.71-0.99). The CT accuracy for the two readers was 0.42 (95% CI, 0.26-0.58) and 0.66 95% CI, 0.43-0.89), respectively. Fluid-attenuated inversion-recovery images improved the conspicuity of SAH on MR images and, along with spin-density-weighted spin-echo sequences, helped to establish the hemorrhagic nature. For parenchymal hemorrhage, the MR accuracy for reader 1 was 0.90 (95% CI, 0.81-0.99); for reader 2, accuracy was 0.93 (95% CI, 0.84-1.00). With CT, the accuracy of reader 1 was 0.91 (95% CI, 0.85-0.97) whereas for reader 2 accuracy was 0.76 (95% CI, 0.69-.83). Parenchymal hemorrhage detection and diagnosis was best with T2*-weighted gradient-echo images., Conclusion: MR imaging with appropriately selected sequences appears able to provide information regarding the presence (or absence) of hemorrhage in an acute stroke model requisite to the initiation of treatment.
- Published
- 1999
21. Segmented three-dimensional echo-planar flow imaging of the cervical carotid arteries.
- Author
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Tkach JA, Ding X, Ruggieri PM, Obuchowski NA, Lieber M, and Masaryk TJ
- Subjects
- Adult, Aged, Arteriosclerosis diagnosis, Blood Flow Velocity physiology, Carotid Artery Diseases diagnosis, Carotid Stenosis diagnosis, Female, Humans, Image Enhancement instrumentation, Male, Middle Aged, Observer Variation, Reference Values, Carotid Arteries anatomy & histology, Echo-Planar Imaging instrumentation, Image Processing, Computer-Assisted instrumentation, Magnetic Resonance Angiography instrumentation
- Abstract
Purpose: To implement and assess the application of segmented three-dimensional echo-planar MR imaging time-of-flight flow sequences for studying the anatomy of the cervical carotid arteries at 1.5 T., Methods: The 3-D echo-planar sequences were segmented along the in-plane phase-encoding direction. Echo train lengths (ETLs) of 3 and 5 and signal bandwidths of +/-25, +/-33, and +/-50 KHz were tested along with a conventional (ETL = 1) 3-D MR flow study in six healthy volunteers and in five patients with known arteriosclerotic disease involving the carotid bifurcation as confirmed by conventional angiography. The volunteer data were used to rank the techniques with respect to vessel dimension, vessel/background contrast, and quality by four trained neuroradiologists. For the patient studies, the percentage of stenoses was measured for all MR studies and compared against the conventional angiographic data using the criteria of the North American Symptomatic Carotid Endarterectomy Trial., Results: Using Wilcoxon's test statistic and a significance level of .05, we found that the conventional MR flow examination was better than the segmented techniques and that the segmented techniques with ETL of 3 were superior to their counterparts with ETL of 5. For the ETL of 3 techniques, the high-bandwidth studies were inferior to their lower bandwidth counterparts; however, there was no significant difference between the performance of the medium- and low-bandwidth sequences. The patient data revealed that the segmented techniques consistently overestimated the severity of stenosis; however, in no instance did any of the segmented examinations erroneously indicate the presence of disease., Conclusions: The reduction in acquisition time and the zero false-positive rate we obtained suggest that segmented 3-D echo-planar MR flow techniques may be used as a screening/locating study for cervical carotid artery disease.
- Published
- 1997
22. Fast spin-echo imaging of the neck: comparison with conventional spin-echo, utility of fat suppression, and evaluation of tissue contrast characteristics.
- Author
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Lewin JS, Curtin HD, Ross JS, Weissman JL, Obuchowski NA, and Tkach JA
- Subjects
- Adipose Tissue pathology, Artifacts, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms pathology, Humans, Hypopharyngeal Neoplasms diagnosis, Hypopharyngeal Neoplasms pathology, Lymph Nodes pathology, Lymphatic Metastasis, Mouth Neoplasms diagnosis, Mouth Neoplasms pathology, Oropharyngeal Neoplasms diagnosis, Oropharyngeal Neoplasms pathology, Carcinoma, Squamous Cell diagnosis, Head and Neck Neoplasms diagnosis, Image Enhancement methods, Magnetic Resonance Imaging methods
- Abstract
Purpose: To determine whether fast spin-echo sequences could replace conventional spin-echo methods in the evaluation of head and neck neoplasms and associated adenopathy and to evaluate differences in tissue contrast characteristics between conventional spin-echo and fast spin-echo examinations of head and neck disease., Methods: Twenty-seven patients with squamous cell carcinoma were imaged on a 1.5-T imager with both conventional spin-echo and fast spin-echo sequences with identical section thickness and position. Twenty-one of the 27 fast spin-echo studies were performed with frequency-selective fat suppression. Three radiologists independently evaluated the images using a five-point scale to compare primary lesion margin definition and conspicuity, lymph node margin definition and conspicuity, gross motion artifact, and flow artifact. Quantitative percent contrast and contrast-to-noise ratios were calculated and compared in 7 cases with fat-suppressed fast spin-echo., Results: Fast spin-echo was preferred by all three readers for lesion margin conspicuity and lymph node conspicuity. Gross motion and flow artifact demonstrated trends toward reader preference for fast spin-echo. Quantitative contrast values for fast spin-echo were significantly greater than those for conventional spin-echo., Conclusions: Fast spin-echo with fat suppression can replace conventional spin-echo at a time savings of more than 50% and improves tissue contrast and the conspicuity and definition of margins for primary lesions and lymph nodes. Fat-suppression heterogeneity remains the major limitation of this technique. Thus, careful attention to fat-suppression failure and unwanted water saturation is essential.
- Published
- 1994
23. Lumbar degenerative disk disease: prospective comparison of conventional T2-weighted spin-echo imaging and T2-weighted rapid acquisition relaxation-enhanced imaging.
- Author
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Ross JS, Ruggieri P, Tkach J, Obuchowski N, Dillinger J, Masaryk TJ, and Modic MT
- Subjects
- Artifacts, Humans, Intervertebral Disc Displacement diagnosis, Prospective Studies, Spinal Stenosis diagnosis, Spondylolisthesis diagnosis, Intervertebral Disc, Magnetic Resonance Imaging methods, Spinal Diseases diagnosis
- Abstract
Purpose: To compare conventional T2-weighted spin-echo imaging with a rapid acquisition relaxation enhanced (RARE) technique in the routine evaluation of lumbar degenerative disk disease., Methods: Thirty consecutive patients referred for evaluation of the lumbar spine for suspected degenerative disk disease were evaluated with sagittal and axial T1-weighted spin-echo, conventional T2-weighted spin-echo, and T2-weighted RARE "turbo spin-echo" sequences (4000/93/2 (repetition time/echo time/excitations), 192 x 256, echo train length of 8). Conventional T2-weighted and RARE images were evaluated independently by two neuroradiologists for image quality, presence of artifacts, cerebrospinal fluid signal intensity, extradural interface conspicuity, intradural nerve root conspicuity, soft-tissue detail, and signal intensity of normal and degenerated intervertebral disks., Results: Both readers rated the cerebrospinal fluid signal higher, the extradural interface conspicuity higher, and the nerve root detail greater on the turbo spin-echo than on conventional spin-echo images. Neither reader had a significant difference in ranking "normal" or "degenerated" disk signal on the two sequences. Both readers rated soft-tissue detail higher for conventional than for turbo spin-echo., Conclusion: RARE sequences can replace conventional T2-weighted spin-echo sagittal studies for degenerative lumbar disk disease.
- Published
- 1993
24. Gd-DTPA-enhanced 3D MR imaging of cervical degenerative disk disease: initial experience.
- Author
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Ross JS, Ruggieri PM, Tkach JA, Masaryk TJ, Paranandi L, Dillinger JJ, and Modic MT
- Subjects
- Female, Gadolinium DTPA, Humans, Male, Middle Aged, Organometallic Compounds, Pentetic Acid, Prospective Studies, Spinal Diseases epidemiology, Cervical Vertebrae, Contrast Media, Gadolinium, Image Processing, Computer-Assisted, Intervertebral Disc pathology, Magnetic Resonance Imaging methods, Spinal Diseases diagnosis
- Abstract
Purpose: To assess whether a single enhanced T1-weighted gradient echo volume sequence, with the appropriate reformatted images, could be equivalent to a more conventional 2D set of MR sequences for the evaluation of cervical extradural degenerative disk disease (bony canal and foraminal stenosis; disk herniation)., Materials and Methods: Sixty-one patients evaluated for extradural degenerative disease by MR were imaged with a "standard" MR examination (Sagittal T1-weighted spin echo, axial low flip angle gradient echo), were then given 0.1 mmol/kg Gd-DTPA intravenously, and reimaged with either a 3D FLASH (fast low angle shot), TR 40/TE 7/1 excitation), 40 degree flip angle, acquired as 64, 2-mm sagittal partitions, or a 3D turbo FLASH (MP RAGE-magnetization prepared rapid acquisition gradient echo) (10/4/1), 10 degree flip angle acquired as 128, 2-mm coronal partitions. The volume sequences were reconstructed in the axial plane, and right and left 45 degree oblique coronal planes. The two sets of examinations (standard vs volume) were prospectively interpreted by two neuroradiologists for quality of examination, and location, type, and severity of extradural degenerative disease in a random, blinded, independent fashion., Results: There was no significant difference between the standard examination and the 3D MP RAGE for central extradural disease. The 3D FLASH examination was significantly worse than the standard examination in identification of central extradural disease, with an average of 21 herniations not identified, or underestimated in size. Neither the 3D FLASH, nor the 3D MP RAGE examinations showed any significant improvement compared to the routine 2D examination for the location and severity of foraminal disease., Conclusion: If extradural degenerative disk disease is being evaluated, then a single enhanced 3D T1-weighted imaging sequence taking 6 minutes can be equivalent to a routine set of mixed 2D spin echo and low flip angle gradient echo sequences.
- Published
- 1992
25. The value of fast gradient-echo MR sequences in the evaluation of brain disease.
- Author
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Steinberg PM, Ross JS, Modic MT, Tkach J, Masaryk TJ, and Haacke EM
- Subjects
- Brain Diseases pathology, Brain Neoplasms diagnosis, Brain Neoplasms pathology, Humans, Magnetic Resonance Imaging methods, Brain Diseases diagnosis
- Abstract
One-hundred-fifteen patients thought to have intracranial disease were studied with various two-dimensional short repetition time, partial-flip-angle gradient-echo techniques: at 1.0 T, fast low-angle short (FLASH) at 10 degrees and 30 degrees and fast imaging with steady-state precession (FISP) at 60 degrees; at 1.5 T, FLASH 10 degrees, 30 degrees, and 60 degrees, FISP 60 degrees, and contrast-enhanced fast steady state at 60 degrees. These sequences were compared with a T2-weighted spin-echo sequence to determine the relative sensitivities of these techniques in detecting parenchymal lesions. Except for hemorrhagic lesions a substantial number of abnormalities were either not visible or poorly seen on the partial-flip-angle gradient-echo sequences. Minimizing echo time (6-9 msec) to decrease magnetic susceptibility effects did not improve lesion detection. Current usage of two-dimensional gradient-echo techniques for lesion detection is limited, except when calcification or hemorrhage is involved. Their utility may be expanded via the incorporation of three-dimensional techniques and IV contrast agents.
- Published
- 1990
26. My quick route to a tough diagnosis.
- Author
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Tkach JR
- Subjects
- Hospital Bed Capacity, 100 to 299, Montana, United States, Diagnosis, Computer-Assisted methods, MEDLARS
- Published
- 1985
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