Current Research and Scholarly Interests
Dr. Atlas has authored more than 120 scientific publications in leading journals. His research has centered on advanced applications of new MRI technologies in neurologic diseases. He has lectured throughout the world on a variety of topics, most notably advances in MRI of the brain, and the key economic issues related to the future of such technology-based advances.
Dr. Atlas's research interests as a Senior Fellow at Hoover center on issues pertaining to public policy in health care. He is investigating the role of government in the emerging era of consumerism in health care, both within the United States and globally, and the impact of government policies on technology-based innovations in medicine. At the Freeman-Spogli Institute for International Studies, he has particular interests in the evolving health care system of emerging economies, and has a recent Fulbright award to collaborate with academic leaders in China on structuring health care solutions for China. Dr. Atlas is also participating with leaders from government and academia on the World Banks Commission on Growth and Development.
Med Scholar Project Advisor
Ultra-high resolution diffusion tensor imaging of the microscopic pathways of the medial temporal lobe
2012; 62 (3): 2065-2082
Diseases involving the medial temporal lobes (MTL) such as Alzheimer's disease and mesial temporal sclerosis pose an ongoing diagnostic challenge because of the difficulty in identifying conclusive imaging features, particularly in pre-clinical states. Abnormal neuronal connectivity may be present in the circuitry of the MTL, but current techniques cannot reliably detect those abnormalities. Diffusion tensor imaging (DTI) has shown promise in defining putative abnormalities in connectivity, but DTI studies of the MTL performed to date have shown neither dramatic nor consistent differences across patient populations. Conventional DTI methodology provides an inadequate depiction of the complex microanatomy present in the medial temporal lobe because of a typically employed low isotropic resolution of 2.0-2.5 mm, a low signal-to-noise ratio (SNR), and echo-planar imaging (EPI) geometric distortions that are exacerbated by the inhomogeneous magnetic environment at the skull base. In this study, we pushed the resolving power of DTI to near-mm isotropic voxel size to achieve a detailed depiction of mesial temporal microstructure at 3 T. High image fidelity and SNR at this resolution are achieved through several mechanisms: (1) acquiring multiple repetitions of the minimum field of view required for hippocampal coverage to boost SNR; (2) utilizing a single-refocused diffusion preparation to enhance SNR further; (3) performing a phase correction to reduce Rician noise; (4) minimizing distortion and maintaining left-right distortion symmetry with axial-plane parallel imaging; and (5) retaining anatomical and quantitative accuracy through the use of motion correction coupled with a higher-order eddy-current correction scheme. We combined this high-resolution methodology with a detailed segmentation of the MTL to identify tracks in all subjects that may represent the major pathways of the MTL, including the perforant pathway. Tractography performed on a subset of the data identified similar tracks, although they were lesser in number. This detailed analysis of MTL substructure may have applications to clinical populations.
View details for DOI 10.1016/j.neuroimage.2012.05.065
View details for Web of Science ID 000307369000073
View details for PubMedID 22677150
Exposure to Ionizing Radiation and Estimate of Secondary Cancers in the Era of High-Speed CT Scanning: Projections From the Medicare Population
JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
2012; 9 (4): 245-250
The aims of this study were to analyze the distribution and amount of ionizing radiation delivered by CT scans in the modern era of high-speed CT and to estimate cancer risk in the elderly, the patient group most frequently imaged using CT scanning.A retrospective cohort study was conducted using Medicare claims spanning 8 years (1998-2005) to assess CT use. The data were analyzed in two 4-year cohorts, 1998 to 2001 (n = 5,267,230) and 2002 to 2005 (n = 5,555,345). The number and types of CT scans each patient received over the 4-year periods were analyzed to determine the percentage of patients exposed to threshold radiation of 50 to 100 mSv (defined as low) and >100 mSv (defined as high). The National Research Council's Biological Effects of Ionizing Radiation VII models were used to estimate the number of radiation-induced cancers.CT scans of the head were the most common examinations in both Medicare cohorts, but abdominal imaging delivered the greatest proportion (43% in the first cohort and 40% in the second cohort) of radiation. In the 1998 to 2001 cohort, 42% of Medicare patients underwent CT scans, with 2.2% and 0.5% receiving radiation doses in the low and high ranges, respectively. In the 2002 to 2005 cohort, 50% of Medicare patients received CT scans, with 4.2% and 1.2% receiving doses in the low and high ranges. In the two populations, 1,659 (0.03%) and 2,185 (0.04%) cancers related to ionizing radiation were estimated, respectively.Although radiation doses have been increasing along with the increasing reliance on CT scans for diagnosis and therapy, using conservative estimates with worst-case scenario methodology, the authors found that the risk for secondary cancers is low in older adults, the group subjected to the most frequent CT scanning. Trends showing increasing use, however, underscore the importance of monitoring CT utilization and its consequences.
View details for DOI 10.1016/j.jacr.2011.12.007
View details for Web of Science ID 000305449600010
View details for PubMedID 22469374
The Worst Study Ever?
2011; 131 (4): 27-32
View details for Web of Science ID 000288586600008
Assessing Cost-Effectiveness And Value As Imaging Grows: The Case Of Carotid Artery CT
2010; 29 (12): 2260-2267
Computed tomographic (CT) angiography is an imaging test that is safer and less expensive than an older test in diagnosing narrowing of the carotid arteries-the most common cause of stroke in US adults. Our examination of Medicare data between 2001 and 2005 found that about 20 percent of the time this test was used, it substituted for the older test. The majority of new use, however, constituted "incremental" use, in cases where patients previously would not have received any test. We found no evidence that the growth in CT angiography led to more patients' being treated for carotid artery disease. The value of the test as a substitute for the older procedure may be enough to still justify expanding use. Tracking the uses of emerging technologies to encourage efficient use is essential, but it can be challenging in cases where new tools have multiple uses and information is incomplete.
View details for DOI 10.1377/hlthaff.2010.0046
View details for Web of Science ID 000285016000017
View details for PubMedID 21134928
Challenges of High-resolution Diffusion Imaging of the Human Medial Temporal Lobe in Alzheimer Disease.
Topics in magnetic resonance imaging
2010; 21 (6): 355-365
The human medial temporal lobe performs an essential role in memory formation and retrieval. Diseases involving the hippocampus such as Alzheimer disease present a unique opportunity for advanced imaging techniques to detect abnormalities at an early stage. In particular, it is possible that diffusion imaging will measure abnormal microarchitecture beyond the realm of macroscopic imaging. However, this task is formidable because of the detailed anatomy of the medial temporal lobe, the difficulties in obtaining high-quality diffusion images of adequate resolution, and the challenges in diffusion data processing. Moreover, it is unclear if any differences will be significant for an individual patient or simply groups of patients. Successful endeavors will need to address each of these challenges in an integrated fashion. The rewards of such analysis may be detection of microscopic disease in vivo, which could represent a landmark accomplishment for the field of neuroradiology.
View details for DOI 10.1097/RMR.0b013e31823f6413
View details for PubMedID 22158129
Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
2009; 51 (7): 526-535
The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.
View details for DOI 10.1111/j.1469-8749.2008.03231.x
View details for Web of Science ID 000266696900007
View details for PubMedID 19459915
Expanded Use Of Imaging Technology And The Challenge of Measuring Value
2008; 27 (6): 1467-1478
The availability of computed tomography (CT) and magnetic resonance imaging (MRI) scanning has grown rapidly, but the value of increased availability is not clear. We document the relationship between CT and MRI availability and use, and we consider potentially important sources of benefits. We discuss key questions that need to be addressed if value is to be well understood. In an example we study, expanded imaging may be valuable because it provides quicker access to more precise diagnostic information, although evidence for improved health outcomes is limited. This may be a common situation; thus, a particularly important question is how non-health-outcome benefits of imaging can be quantified.
View details for DOI 10.1377/hlthaff.27.6.1467
View details for Web of Science ID 000260769300003
View details for PubMedID 18997202
Embracing subspecialization: the key to the survival of radiology.
Journal of the American College of Radiology
2007; 4 (11): 752-753
View details for PubMedID 17964496
Advertising, patient decision making, and self-referral for computed tomographic and magnetic resonance imaging
ARCHIVES OF INTERNAL MEDICINE
2004; 164 (22): 2415-2419
Self-referred imaging is one of the latest health care services to be marketed directly to consumers. Most aspects of these services are unregulated, and little is known about the messages in advertising used to attract potential consumers. We conducted a detailed analysis of print advertisements and informational brochures for self-referred imaging with respect to themes, content, accuracy, and emotional valence.Forty print advertisements from US newspapers around the country and 20 informational brochures were analyzed by 2 independent raters according to 7 major themes: health care technology; emotion, empowerment, and assurance; incentives; limited supporting evidence; popular appeal; statistics; and images. The Fisher exact test was used to identify significant differences in information content.Both the advertisements and the brochures emphasized health care and technology information and provided assurances of good health and incentives to self-refer. These materials also encouraged consumers to seek further information from company resources; virtually none referred to noncomplying sources of information or to the risks of having a scan. Images of people commonly portrayed European Americans. We found statistical differences between newspaper advertisements and mailed brochures for references to "prevalence of disease" (P<.001), "death" (P<.003), and "radiation" (P<.001). Statements lacking clear scientific evidence were identified in 38% of the advertisements (n = 15) and 25% of the brochures (n = 5).Direct-to-consumer marketing of self-referred imaging services, in both print advertisements and informational brochures, fails to provide prospective consumers with comprehensive balanced information vital to informed autonomous decision making. Professional guidelines and oversight for advertising and promotion of these services are needed.
View details for Web of Science ID 000225701900003
View details for PubMedID 15596630
Discovery and disclosure of incidental findings in neuroimaging research
JOURNAL OF MAGNETIC RESONANCE IMAGING
2004; 20 (5): 743-747
To examine different protocols for handling incidental findings on brain research MRIs, and provide a platform for establishing formal discussions of related ethical and policy issues.Corresponding authors identified from a database of peer-reviewed publications in 1991-2002 involving functional MRI (fMRI), alone or in combination with other imaging modalities, were invited to participate in this web-based survey. The survey asked questions regarding knowledge and handling of incidental findings, as well as characteristics of the scanning environment, training required, IRB protocol requirements, and neuroradiologist involvement.Seventy-four investigators who conduct MRI studies in the United States and abroad responded. Eighty-two percent (54/66) reported discovering incidental findings in their studies, such as arteriovenous malformations, brain tumors, and developmental abnormalities. Substantial variability was found in the procedures for handling and communicating findings to subjects, neuroradiologist involvement, personnel permitted to operate equipment, and training.Guidelines for minimum and optimum standards for detecting and communicating incidental findings on brain MRI research are needed.
View details for DOI 10.1002/jmri.20180
View details for Web of Science ID 000224762700001
View details for PubMedID 15503329
Relationship between HMO market share and the diffusion and use of advanced MRI technologies.
Journal of the American College of Radiology
2004; 1 (7): 478-487
Financial incentives associated with managed care may shift incentives associated with the adoption of new medical technologies. This study examined whether managed-care activity was associated with the adoption rate of magnetic resonance imaging (MRI) equipment during the 1990s.Data from three nationwide "censuses" of MRI sites conducted in 1993, 1997, and 1999 were used. The number of MRI sites and magnets; magnet field strength; MRI procedures; the use of contrast media; and the presence of power injectors, echoplanar imaging, cardiac MRI, and interventional MRI were measured in each of 322 metropolitan statistical areas each year. Regression analysis was used to assess the relationship between area MRI availability and overall area health maintenance organization (HMO) market share, controlling for potential confounders.Areas with higher HMO activity had markedly lower adoption and use of MRI. By 1999, high-HMO areas had about 40% fewer MRI scanners per 100,000 people than low-HMO areas (1.02 vs. 1.73, P < .01). High-HMO areas had fewer 1.5-T scanners than low areas in all 3 years and tended to use contrast media less often in 1993 and 1997 (all P < .01). There were statistically insignificant trends toward less availability of echoplanar imaging, cardiac MRI, and interventional MRI in high-HMO areas.The fact that managed care is associated with the slower adoption of MRI and less availability of some of the most advanced MRI equipment suggests the need for attention to the potential for managed care to have important effects on the quality of care and health care spending by influencing technology growth.
View details for PubMedID 17411636
Ethical consideration of incidental findings on adult brain MRI in research
2004; 62 (6): 888-890
To characterize the frequency and severity of incidental findings in brain MRIs of young and older adult research volunteers, and to provide an evaluation of the ethical challenges posed by the detection of such findings.The authors reviewed 151 research MRI scans obtained retrospectively from subjects recruited to studies as healthy volunteers. Incidental findings were classified into four categories: no referral, routine, urgent, or immediate referral. p Values for significance were computed from chi(2) tests of contingency.Of 151 studies, the authors found an overall occurrence of incidental findings having required referral of 6.6%. By age, there were more findings in the older cohort (aged >60 years) than in the younger cohort (p < 0.05) and in more men than women in the older cohort (p < 0.001). Three of four (75%) findings in the younger cohort were classified in the urgent referral category; 100% of the findings in the older cohort were classified as routine (p < 0.05).The significant presence but different characteristics of incidental findings in young and older subjects presumed to be neurologically healthy suggest that standards of practice are needed to guide investigators in managing and communicating their discovery.
View details for Web of Science ID 000220365300010
View details for PubMedID 15037687
Magnetic resonance image-guided proteomics of human glioblastoma multiforme
JOURNAL OF MAGNETIC RESONANCE IMAGING
2003; 18 (5): 530-536
To investigate the correlation between gadolinium contrast-enhancement patterns on T1-weighted magnetic resonance (MR) images and spatial changes in protein expression profiles in human glioblastoma multiforme (GBM) and the use of imaging as a noninvasive technique to evaluate the heterogeneity of solid tumors prior to microarray analysis.Four patients with MR images and confirmed diagnosis of GBM were enrolled in the study. Intraoperative stereotaxy was used in conjunction with MR images to identify contrast-enhanced (CE) and nonenhanced (NE) regions of the tumor during surgical resection. Total protein was extracted from resected tumor samples using standard techniques and subjected to proteomic analysis using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS).We found that protein profiles from CE and NE regions within a given tumor have qualitative and semiquantitative proteomic pattern differences, suggesting an altered gene expression profile that correlates with detectable tissue imaging parameters. We also found that CE regions within the same tumor exhibited distinct differences in protein expression profiles, despite similar histological features. In addition, there were marked similarities in the proteomic patterns among the NE regions across all patients, while the CE regions were distinct, suggesting that the CE regions have complex protein profiles unique to individuals.The results demonstrate that major differences in protein expression patterns within a tumor can be correlated to radiographic findings. Image-guided proteomics holds promise for characterizing tissue prior to microarray analysis designed to identify specific diagnostic markers and therapeutic targets within solid tumors.
View details for DOI 10.1002/jmri.10395
View details for Web of Science ID 000186295300002
View details for PubMedID 14579395
Gray matter-N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis
AMERICAN JOURNAL OF NEURORADIOLOGY
2003; 24 (10): 1941-1945
Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS.Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately.Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations.The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.
View details for Web of Science ID 000186744800006
View details for PubMedID 14625214
Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants
AMERICAN JOURNAL OF NEURORADIOLOGY
2003; 24 (8): 1646-1653
Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings.We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age.Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes.These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.
View details for Web of Science ID 000185400100031
View details for PubMedID 13679287
Self-referred whole-body CT imaging: Current implications for health care consumers
2003; 228 (2): 346-351
To conduct an empirical analysis of self-referred whole-body computed tomography (CT) and develop a profile of the geographic and demographic distribution of centers, types of services and modalities, costs, and procedures for reporting results.An analysis was conducted of Web sites for imaging centers accepting self-referred patients identified by two widely used Internet search engines with large indexes. These Web sites were analyzed for geographic location, type of screening center, services, costs, and procedures for managing imaging results. Demographic data were extrapolated for analysis on the basis of center location. Descriptive statistics, such as frequencies, means, SDs, ranges, and CIs, were generated to describe the characteristics of the samples. Data were compared with national norms by using a distribution-free method for calculating a 95% CI (P <.05) for the median.Eighty-eight centers identified with the search methods were widely distributed across the United States, with a concentration on both coasts. Demographic analysis further situated them in areas of the country characterized by a population that consisted largely of European Americans (P <.05) and individuals of higher education (P <.05) and socioeconomic status (P <.05). Forty-seven centers offered whole-body screening; heart and lung examinations were most frequently offered. Procedures for reporting results were highly variable.The geographic distribution of the centers suggests target populations of educated health-conscious consumers who can assume high out-of-pocket costs. Guidelines developed from within the profession and further research are needed to ensure that benefits of these services outweigh risks to individuals and the health care system.
View details for DOI 10.1148/radiol.2282021083
View details for Web of Science ID 000184381100010
View details for PubMedID 12893896