Right arcuate fasciculus abnormality in chronic fatigue syndrome.

PURPOSE: To identify whether patients with chronic fatigue syndrome (CFS) have differences in gross brain structure, microscopic structure, or brain perfusion that may explain their symptoms. MATERIALS AND METHODS: Fifteen patients with CFS were identified by means of retrospective review with an institutional review board-approved waiver of consent and waiver of authorization. Fourteen age- and sex-matched control subjects provided informed consent in accordance with the institutional review board and HIPAA. All subjects underwent 3.0-T volumetric T1-weighted magnetic resonance (MR) imaging, with two diffusion-tensor imaging (DTI) acquisitions and arterial spin labeling (ASL). Open source software was used to segment supratentorial gray and white matter and cerebrospinal fluid to compare gray and white matter volumes and cortical thickness. DTI data were processed with automated fiber quantification, which was used to compare piecewise fractional anisotropy (FA) along 20 tracks. For the volumetric analysis, a regression was performed to account for differences in age, handedness, and total intracranial volume, and for the DTI, FA was compared piecewise along tracks by using an unpaired t test. The open source software segmentation was used to compare cerebral blood flow as measured with ASL. RESULTS: In the CFS population, FA was increased in the right arcuate fasciculus (P = .0015), and in right-handers, FA was also increased in the right inferior longitudinal fasciculus (ILF) (P = .0008). In patients with CFS, right anterior arcuate FA increased with disease severity (r = 0.649, P = .026). Bilateral white matter volumes were reduced in CFS (mean ± standard deviation, 467 581 mm(3) ± 47 610 for patients vs 504 864 mm(3) ± 68 126 for control subjects, P = .0026), and cortical thickness increased in both right arcuate end points, the middle temporal (T = 4.25) and precentral (T = 6.47) gyri, and one right ILF end point, the occipital lobe (T = 5.36). ASL showed no significant differences. CONCLUSION: Bilateral white matter atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.

Ultra-high resolution diffusion tensor imaging of the microscopic pathways of the medial temporal lobe.

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.

Exposure to ionizing radiation and estimate of secondary cancers in the era of high-speed CT scanning: projections from the Medicare population.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessing cost-effectiveness and value as imaging grows:the case of carotid artery CT.

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.

Challenges of High-resolution Diffusion Imaging of the Human Medial Temporal Lobe in Alzheimer Disease.

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.

Arterial spin-label imaging in patients with normal bolus perfusion-weighted MR imaging findings: pilot identification of the borderzone sign.

PURPOSE: To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings. MATERIALS AND METHODS: Institutional review board approval and written informed patient consent were obtained. This study was HIPAA compliant. Consecutive patients suspected or known to have cerebrovascular disease underwent 1.5-T brain MR imaging, including MR angiography, gradient-echo PW imaging, and pseudocontinuous ASL imaging, between October 2007 and January 2008. Patients with normal bolus PW imaging findings were retrospectively identified, and two neuroradiologists subsequently evaluated the ASL images for focal abnormalities. The severity of the borderzone sign-that is, bilateral ASL signal dropout with surrounding cortical areas of hyperintensity in the middle cerebral artery borderzone regions-was classified by using a four-point scale. For each group, the ASL-measured mean mixed cortical cerebral blood flow (CBF) at the level of the centrum semiovale was evaluated by using the Jonckheere-Terpstra test. RESULTS: One hundred thirty-nine patients met the study inclusion criteria, and 41 (30%) of them had normal bolus PW imaging findings. Twenty-three (56%) of these 41 patients also had normal ASL imaging findings. The remaining 18 (44%) patients had the ASL borderzone sign; these patients were older (mean age, 71 years +/- 11 [standard deviation] vs 57 years +/- 16; P < .005) and had lower mean CBF (30 mL/100 g/min +/- 12 vs 46 mL/100 g/min +/- 12, P < .003) compared with the patients who had normal ASL imaging findings. Five patients had additional focal ASL findings that were related to either slow blood flow in a vascular structure or postsurgical perfusion defects and were not visible on the PW images. CONCLUSION: Approximately half of the patients with normal bolus PW imaging findings had abnormal ASL findings-most commonly the borderzone sign. Results of this pilot study suggest that ASL imaging in patients who have this sign and are suspected of having cerebrovascular disease yields additional and complementary hemodynamic information.

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

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.

Expanded use of imaging technology and the challenge of measuring value.

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.

Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.

We describe the clinical course of a patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system, developed during treatment with interferon beta-1a and a selective adhesion-molecule blocker, natalizumab. The first PML lesion apparent on magnetic resonance imaging was indistinguishable from a multiple sclerosis lesion. Despite treatment with corticosteroids, cidofovir, and intravenous immune globulin, PML progressed rapidly, rendering the patient quadriparetic, globally aphasic, and minimally responsive. Three months after natalizumab therapy was discontinued, changes consistent with an immune-reconstitution inflammatory syndrome developed. The patient was treated with systemic cytarabine, and two months later, his condition had improved.

The prevalence of microhemorrhage on gradient-echo magnetic resonance imaging in acute lacunar infarction.

INTRODUCTION: Microhemorrhages seen on gradient-echo magnetic resonance imaging are thought to be a manifestation of small-vessel disease. It was the aim of our study to evaluate the prevalence of microhemorrhage for patients presenting with acute lacunar infarction. METHODS: We obtained gradient-echo and diffusion-weighted magnetic resonance imaging as part of the acute stroke workup in 46 patients presenting with lacunar infarction. RESULTS: Gradient-echo magnetic resonance imaging was abnormal in 24 of 46 (52%) patients. Microhemorrhage was seen in 21 patients (46%), 2 patients had multiple microhemorrhages and a frank hemorrhage, and 3 patients had frank hemorrhage in the absence of microhemorrhage. Prior symptomatic stroke was the only significant risk factor for the presence of microhemorrhages. CONCLUSION: Microhemorrhages are present in approximately half of patients with lacunar infarcts and appear to be a marker of severity of small-vessel disease.

Advertising, patient decision making, and self-referral for computed tomographic and magnetic resonance imaging.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Discovery and disclosure of incidental findings in neuroimaging research.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Guidelines for minimum and optimum standards for detecting and communicating incidental findings on brain MRI research are needed.

Relationship between HMO market share and the diffusion and use of advanced MRI technologies.

BACKGROUND: 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 AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Female sexual arousal: a behavioral analysis.

OBJECTIVE: This study was designed to assess female sexual arousal by using a combination of physiologic measures and self-reported level of arousal. DESIGN: Twenty subjects viewed a 23-minute sequence of randomly ordered relaxation and erotic tapes, both with and without auditory stimulus. The physiologic parameters of vaginal blood flow, galvanic skin resistance, respiration, pulse, and blood pressure, as well as self-reported level of arousal, were simultaneously recorded and correlated with video segments. SETTING: An academic teaching hospital. PATIENT(S): The 20 subjects (mean age +/- SD: 24.9 +/- 3.0 years) included Caucasian (10), Hispanic (2), Asian-American (4), and African-American (4) women. All women were screened for normal sexual function with the Female Sexual Function Index (FSFI) and with the Beck Anxiety Inventory and Beck Depression Inventory. INTERVENTION(S): Randomly ordered sequences of erotic and relaxation tapes with and without sound. MAIN OUTCOME MEASURE(S): Physiologic and behavioral data, as well as subjective arousal rating, were acquired. The resulting set of multichannel data was correlated with erotic segments and analyzed for sound vs. no sound and time to maximal physiologic arousal. RESULT(S): Four independent variables were found to have beta values that were significantly different from 0: respiration (mean = -0.239, SD = 0.177, range = -0.55-0.09, t = -6.04), VPP (mean = 0.158, SD = 0.37, range = -0.48-0.80, t = 1.91), rVPP (mean = 0.161, SD = 0.35, range = -0.537-0.686, t = 2.075), and erotic marker (mean = 0.582, SD = 0.191, range = 0.16-0.85, t = 13.6). Neither heart rate nor galvanic skin resistance beta values approached significance. Respiration period was correlated negatively with arousal rating, indicating that subjects breathed faster when aroused. Auditory stimuli during erotic segments did not increase subjective arousal, and for both subjective arousal rating as well as VPP measurement, maximal response occurred within 2 minutes. CONCLUSION(S): Simultaneous measurement of vaginal blood flow, respiration, pulse, and a variable accounting for the onset and offset of erotic video segments accounts for approximately 50% of the variance in predicting subjective female arousal. Regardless of the presence or absence of audio input, 2 minutes was the average minimum time required to reach maximal arousal in young, sexually functional women.