Effect of formalin fixation on measured concentrations of deposited gadolinium in human tissue: an autopsy study.

BACKGROUND: Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated. PURPOSE: To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues. MATERIAL AND METHODS: Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS. RESULTS: Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation (P = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month (P = 0.11) and 6.0% (P = 0.73) between one and three months. CONCLUSION: Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%-40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.

Comparison of Human Tissue Gadolinium Retention and Elimination between Gadoteridol and Gadobenate.

Background Linear gadolinium-based contrast agents (GBCAs) are known to be retained at higher levels of gadolinium than macro-cyclic GBCAs. However, very little is known regarding their relative elimination rates and retained fraction of injected gadolinium. Purpose To quantify and compare gadolinium retention and elimination rates in human brain tissue, skin, and bone obtained from cadavers exposed to single-agent administration of either gadoteridol (macrocyclic GBCA) or gadobenate dimeglumine (linear GBCA). Materials and Methods Autopsy cases from August 2014 to July 2019 of patients exposed to a single type of GBCA, either gadoteridol or gadobenate dimeglumine, either single or multiple doses, were included. Gadolinium levels in the brain, skin, and bone were analyzed with inductively coupled plasma mass spectrometry. Linear regression was used to compare gadolinium retention between agents and estimate elimination rates of the retained gadolinium using the time between last injection and death. Results Twenty-eight cadavers with gadoteridol exposure and nine with gadobenate dimeglumine exposure were identified (22 men; age range, 19-83 years). The median gadolinium retention of gadobenate dimeglumine was 3.0-6.5 times higher than that of gadoteridol in the brain (P < .02), 4.4 times higher in bone (P = .002), and 2.9 times higher in skin (P = .05). Gadolinium retention in the globus pallidus (GP), dentate nucleus (DN), white matter (WM), bone, and skin decreased with time elapsed from last administration to death in both the gadobenate dimeglumine (GP: -3% per twofold increase in time, P = .69; DN: -2%, P = .83; WM: -20%, P = .01; bone: -22%, P = .07; skin: -47%, P < .001) and gadoteridol (GP: -17%, P = .11; DN: -16%, P = .15; WM: -30%, P < .001; bone: -11%, P = .16; skin: -24%, P = .01) groups (P values for elimination are compared with a null hypothesis of no elimination). Conclusion The linear agent gadobenate dimeglumine retains several-fold higher levels of gadolinium in the brain and bone compared with the macrocyclic agent gadoteridol. Nonzero elimination of retained gadolinium was detected in the white matter and skin for both agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Variability in hair gadolinium concentrations among decedents who received gadolinium-based contrast agents.

This study utilized laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify gadolinium in the hair of autopsy cases that had received gadolinium-based contrast agents (GBCAs) before death. Consecutive autopsy cases were reviewed for GBCA injections and subjects who received a single type of GBCA in the year before death were included. Hair samples were analyzed using LA-ICP-MS as a line scan technique and parameters were optimized to maximize instrument sensitivity, accuracy, and precision. Linear regression analyses between hair measures and gadolinium dose were executed. LA-ICP-MS analysis produced a time-resolved record of GCBA exposure, with the position of the gadolinium peak maxima along the hair shaft providing a good estimate for the day that GBCA injection occurred (R2 = 0.46; p = 0.0022); however, substantial within and between subject variation in the position of the GBCA peak was observed. Average area under the curve for gadolinium peaks in the hair samples was a better predictor of gadolinium dose (R2 = 0.41; p = 0.0046), compared to the average of peak maxima concentration. Correlation between area under the curve and dose suggests that LA-ICP-MS analysis of hair may be an effective method to evaluate gadolinium levels in subjects in vivo after exposure to GBCAs. This study demonstrates that analysis of human hair using techniques with high spatial resolution such as LA-ICP-MS has excellent potential to reveal time-dependent signatures of past exposures.

Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. RESULTS: Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. CONCLUSION: T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

Brain tissue gadolinium retention in pediatric patients after contrast-enhanced magnetic resonance exams: pathological confirmation.

BACKGROUND: Retained gadolinium from gadolinium-based contrast agents (GBCAs) used in MR exams has been inferred based on signal changes on serial brain MRI and subsequently demonstrated pathologically in adults. Retention has been similarly inferred in children but pathological demonstration in pediatric patients is limited. The long-term effects of retained gadolinium are unknown but are potentially of greater concern in children given their increased vulnerability from continuing development and their expected longer period of exposure. Several factors can influence gadolinium retention. In adults as well as in children, greater accumulation has been demonstrated based on MR signal changes with linear compared with macrocyclic gadolinium chelates, attributed to lower chelate affinity with linear agents. Effects of age at exposure on retention are unknown, while differences in GBCA washout rates are still under investigation and might affect gadolinium retention relative to time of GBCA administration. OBJECTIVE: The purpose of this study was to confirm whether gadolinium brain deposits are present in pediatric patients who received GBCAs and to quantify the amounts present. MATERIALS AND METHODS: Brain autopsy specimens from 10 pediatric patients between 1 year and 13 years of age who underwent at least one contrast-enhanced MR exam were analyzed for elemental gadolinium using inductively coupled plasma mass spectrometry. Brain samples included white matter, basal ganglia (putamen, globus pallidus), thalamus, dentate nucleus and tumor tissue as available. Type and dose of contrast agent, number and timing of contrast-enhanced MR exams and renal function (estimated glomerular filtration rate [eGFR]) were documented for each child. RESULTS: Patient exposures ranged from 1 dose to 20 doses of GBCAs including both macrocyclic and linear ionic agents. Gadolinium was found to be present in brain tissue in all children and was generally highest in the globus pallidus. Those who received only macrocyclic agents showed lower levels of gadolinium retention. CONCLUSION: This study demonstrates pathological confirmation of gadolinium retention in brain tissue of a series of pediatric patients exposed to GBCAs including not only linear ionic agents but also macrocyclic agents with both nonionic and ionic compounds. The distribution and deposition levels in this small pediatric population are comparable with the findings in adults. While the clinical significance of these deposits remains unknown, at this point it would be prudent to exert caution and avoid unnecessary use of GBCAs in pediatric patients.

Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on Gadolinium Chelates.

Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .

Alterations in Connectivity on Functional Magnetic Resonance Imaging with Provocation of Lower Urinary Tract Symptoms: A MAPP Research Network Feasibility Study of Urological Chronic Pelvic Pain Syndromes.

PURPOSE: Urological chronic pelvic pain syndromes have refractory bladder or pelvic pain as the dominant symptom. This has been attributed to changes in the central nervous system caused by a chronic barrage of noxious stimuli. We developed what is to our knowledge a novel challenge protocol that induced bladder distention in study participants to reproduce pain and urinary symptoms. We tested to see whether it could discriminate between persons with urological chronic pelvic pain syndrome-like symptoms and asymptomatic controls. MATERIALS AND METHODS: We recruited 10 female twin pairs who were discordant for urological chronic pelvic pain syndrome-like symptoms. Before scanning each twin urinated to completion and then consumed 500 cc water. Each twin was scanned with our resting state functional magnetic resonance imaging protocol immediately and approximately 50 minutes after consumption. Time series were extracted from the right and left periaqueductal gray, and the right and left amygdala subregions. We performed the repeated measures 2-sample t-test to assess differences in connectivity between symptomatic and asymptomatic twins before and after bladder distention. RESULTS: Group by condition interaction effects were found from the periaqueductal gray to the right cerebellum VIIIa, the amygdala, the right premotor cortex/supplementary motor area and the insular cortex, and between the amygdala and the frontal pole/medial orbital frontal cortex, the hypothalamus, the insular cortex, the thalamus and the anterior cingulate cortex. CONCLUSIONS: These findings demonstrate that our noninvasive bladder distention protocol can detect differences in the processing of urinary sensation between twins discordant for lower urinary tract pain.

Fast whole-brain three-dimensional macromolecular proton fraction mapping in multiple sclerosis.

PURPOSE: To evaluate the clinical utility of fast whole-brain macromolecular proton fraction ( MPF macromolecular proton fraction ) mapping in multiple sclerosis ( MS multiple sclerosis ) and compare MPF macromolecular proton fraction with established quantitative magnetic resonance (MR) imaging measures of tissue damage including magnetization transfer ( MT magnetization transfer ) ratio and relaxation rate (R1). MATERIALS AND METHODS: In this institutional review board-approved and HIPAA-compliant study, 14 healthy control participants, 18 relapsing-remitting MS multiple sclerosis ( RRMS relaxing-remitting MS ) patients, and 12 secondary progressive MS multiple sclerosis ( SPMS secondary progressive MS ) patients provided written informed consent and underwent 3-T MR imaging. Three-dimensional MPF macromolecular proton fraction maps were reconstructed from MT magnetization transfer -weighted images and R1 maps by the single-point method. Mean MPF macromolecular proton fraction , R1, and MT magnetization transfer ratio in normal-appearing white matter ( WM white matter ), gray matter ( GM gray matter ), and lesions were compared between subject groups by using analysis of variance. Correlations (Pearson r) between imaging data and clinical scores (Expanded Disability Status Scale [EDSS] and MS multiple sclerosis Functional Composite [ MSFC MS functional composite ]) were compared by using Hotelling-Williams test. RESULTS: RRMS relaxing-remitting MS patients had lower WM white matter and GM gray matter MPF macromolecular proton fraction than controls, with percentage decreases of 6.5% (P < .005) and 5.4% (P < .05). MPF macromolecular proton fraction in SPMS secondary progressive MS was reduced relative to RRMS relaxing-remitting MS in WM white matter , GM gray matter , and lesions by 6.4% (P < .005), 13.4% (P < .005), and 11.7% (P < .05), respectively. EDSS Expanded Disability Status Scale and MSFC MS functional composite demonstrated strongest correlations with MPF macromolecular proton fraction in GM gray matter (r = -0.74 and 0.81; P < .001) followed by WM white matter (r = -0.57 and 0.72; P < .01) and lesions (r = -0.42 and 0.50; P < .05). R1 and MT magnetization transfer ratio in all tissues were significantly less correlated with clinical scores than GM gray matter MPF macromolecular proton fraction (P < .05). CONCLUSION: MPF macromolecular proton fraction mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of GM gray matter damage in MS multiple sclerosis . MPF macromolecular proton fraction outperforms MT magnetization transfer ratio and R1 in detection of MS multiple sclerosis -related tissue changes.

Brain White Matter Abnormalities in Female Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Neuroimaging Study.

PURPOSE: Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. MATERIALS AND METHODS: We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. RESULTS: Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. CONCLUSIONS: To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

Absent cavum septum pellucidum: a review with emphasis on associated commissural abnormalities.

The cavum septum pellucidum (CSP) is an important fetal midline forebrain landmark, and its absence often signifies additional underlying malformations. Frequently detected by prenatal sonography, absence of the CSP requires further imaging with pre- or postnatal MRI to characterize the accompanying abnormalities. This article reviews the developmental anatomy of the CSP and the pivotal role of commissurization in normal development. An understanding of the patterns of commissural abnormalities associated with absence of the CSP can lead to improved characterization of the underlying spectrum of pathology.

Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from posttreatment effects.

PURPOSE: To compare 3 Tesla (3T) multi-voxel and single-voxel proton MR spectroscopy (MRS), dynamic susceptibility contrast perfusion MRI (DSC), and diffusion-weighted MRI (DWI) for distinguishing recurrent glioma from postradiation injury. MATERIALS AND METHODS: We reviewed all 3T MRS, DSC and DWI studies performed for suspicion of malignant glioma recurrence between October 2006 and December 2008. Maximum Cho/NAA and Cho/Cr peak-area and peak-height ratios were recorded for both multi-voxel and single-voxel MRS. Maximum cerebral blood volume (CBV) and minimum apparent diffusion coefficient (ADC) were normalized to white matter. Histopathology and clinical-radiologic follow-up served as reference standards. Receiver operating characteristic curves for each parameter were compared. RESULTS: Forty lesions were classified as glioma recurrence (n = 30) or posttreatment effect (n = 10). Diagnostic performance was similar for CBV ratio (AUC = 0.917, P < 0.001), multi-voxel Cho/Cr peak-area (AUC = 0.913, P = 0.002), and multi-voxel Cho/NAA peak-height (AUC = 0.913, P = 0.002), while ADC ratio (AUC = 0.726, P = 0.035) did not appear to perform as well. Single-voxel MRS parameters did not reliably distinguish tumor recurrence from posttreatment effects. CONCLUSION: A 3T DSC and multi-voxel MRS Cho/Cr peak-area and Cho/NAA peak-height appear to outperform DWI for distinguishing glioma recurrence from posttreatment effects. Single-voxel MRS parameters do not appear to distinguish glioma recurrence from posttreatment effects reliably, and therefore should not be used in place of multi-voxel MRS.

Influence of sildenafil on genital engorgement in women with female sexual arousal disorder.

INTRODUCTION: We previously described dynamic, noncontrast magnetic resonance imaging (MRI) of the female genitalia as a reproducible, nonintrusive, objective means of quantifying sexual arousal response in women without sexual difficulties. These studies showed an increase in clitoral engorgement ranging from 50 to 300% in healthy women during sexual arousal. AIM: This study sought to evaluate the genital arousal response in women with female sexual arousal disorder (FSAD) after administration of sildenafil and placebo. We performed a multicenter, double-blind, placebo-controlled, cross-over study to assess the clitoral engorgement response using dynamic MRI in women with FSAD after administering sildenafil and placebo followed by audiovisual sexual stimulation (AVSS). METHODS: Nineteen premenopausal women with FSAD underwent two MRI sessions. Subjects were randomized to receive either (i) sildenafil 100 mg during the first session followed by placebo during the second session, or (ii) placebo followed by sildenafil. During each session, baseline MR images were obtained while subjects viewed a neutral video. Subjects then ingested sildenafil or placebo. After 30 minutes, a series of MRIs were obtained at 3-minute intervals for 10 time points while subjects viewed AVSS. MAIN OUTCOME MEASURES: A positive sexual arousal response was achieved if clitoral volume increased ≥50% from baseline. RESULTS: Thirteen of 19 (68%) subjects achieved a ≥50% increase in clitoral engorgement from baseline when administered sildenafil or placebo 30 minutes after dose administration. At 60 minutes after administration, 17/19 (89%) subjects receiving sildenafil and 16/19 (84%) subjects receiving placebo had responded (P value 0.3173). CONCLUSIONS: Sildenafil did not augment the genital response in women with FSAD. Secondarily, a majority of women in this study did not have impaired clitoral engorgement as measured by MRI, suggesting that FSAD is not predominantly a disorder of genital engorgement.

Physiology of women's sexual function: basic knowledge and new findings.

INTRODUCTION: Data concerning the physiology of female sexual functioning are still obtained from animal studies, but an increasing amount of novel evidence comes from human studies. AIM: To gain knowledge of psychological and biologic physiology of women's sexual functioning, mainly addressing sexual arousal and orgasm. METHODS: A broad-based literature review of current knowledge of the psychological and biologic physiology aspects of women's sexual functioning. RESULTS: A comprehensive understanding of the anatomical, neurobiological, and psychological mechanisms behind sexual function and responses is of paramount importance. A biopsychological paradigm was considered when reviewing currently available data, thus considering aspects of: (i) sexual differentiation of the brain, which is critical for sex differentiation in behavior; (ii) central neurobiology of sexual function, highlighting specific and innovative findings from neuroimaging methods that enable visualization of active brain areas during arousal and orgasm; and (iii) peripheral functional anatomy, mainly addressing genital arousal and orgasm. Translational science was also covered, providing data about the actual role of sexual arousal in women in both procreation/reproduction and recreation/pleasure. The interaction between physiological and psychological states of women's sexual response, nonspecific sexual response, interoceptive awareness, and flexibility of sexual interests have also been addressed. CONCLUSION: Further research on normal physiology of women's sexual function is needed in order to expand and "translate" current knowledge into the pathophysiological clinical setting. This manuscript encompasses data presented at the 3rd International Consultation on Sexual Medicine in Paris, France, July 10-13, 2009.

Distinction between glioma progression and post-radiation change by combined physiologic MR imaging.

INTRODUCTION: Magnetic resonance (MR) diffusion-weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion imaging (DSC), and MR spectroscopy (MRS) techniques provide specific physiologic information that may distinguish malignant glioma progression from post-radiation change, yet no single technique is completely reliable. We propose a simple, multiparametric scoring system to improve diagnostic accuracy beyond that of each technique alone. METHODS: Fifteen subjects with lesions suspicious for glioma progression following radiation therapy who had also undergone 3-tesla DWI, DSC, and MRS studies of the lesion were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC) ratio, maximum regional cerebral blood volume (rCBV) ratio, and maximum MRS choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) metabolic peak-height ratios were quantified within each lesion. Each parameter (ADC ratio, rCBV ratio, and combined Cho/Cr and Cho/NAA ratios) was scored as either glioma progression (one point) or radiation change (zero point) based upon thresholds derived from our own data. For each lesion, the combined parameters yielded a multiparametric score (0 to 3) for prediction of tumor progression or post-radiation change. RESULTS: Optimum thresholds for ADC ratio (1.30), rCBV ratio (2.10), and either combined Cho/Cr (1.29) and Cho/NAA (1.06) yielded diagnostic accuracies of 86.7%, 86.7%, and 84.6%, respectively (p < 0.05). A combined multiparametric score threshold of 2 improved diagnostic accuracy to 93.3% (p < 0.05). CONCLUSION: In this small series combining 3-T DWI, DSC, and MRS diagnostic results using a simple, multiparametric scoring system has potential to improve overall diagnostic accuracy in distinguishing glioma progression from post-radiation change beyond that of each technique alone.

Human Hair as a Possible Surrogate Marker of Retained Tissue Gadolinium: A Pilot Autopsy Study Correlating Gadolinium Concentrations in Hair With Brain and Other Tissues Among Decedents Who Received Gadolinium-Based Contrast Agents.

OBJECTIVES: We used laser ablation inductively coupled plasma mass spectrometry to quantify gadolinium in hair samples from autopsy cases with gadolinium-based contrast agent (GBCA) exposure. Hair gadolinium data were correlated with gadolinium concentrations in brain, skin, and bone tissues from the same case to investigate a potential noninvasive method for gadolinium quantification and monitoring. MATERIALS AND METHODS: Medical records from autopsy cases at our institution were screened for history of GBCA exposure. Cases with exposure to a single type of GBCA with the most recent injection occurring within 1 year were identified and included in the study. The concentration of gadolinium in hair samples was analyzed by laser ablation inductively coupled plasma mass spectrometry, and brain (globus pallidus, dentate nucleus, white matter), bone, and skin tissues were analyzed by bulk inductively coupled plasma mass spectrometry. The mean of the maximum value in the hair samples was used to generate a representative measurement of the hair gadolinium concentration for each case. A linear regression analysis between each tissue type and hair was conducted to assess for possible correlation. RESULTS: Tissue and hair samples from 18 autopsies (16 cases with exposure to GBCA, 2 controls) were included in the study. Comparing the different tissues revealed good correlation between some tissue types. The best model fit occurred between white matter and hair (R = 0.83; P < 0.0001) followed by the comparison between dentate nucleus and hair (R = 0.72; P < 0.0001) and dentate nucleus and skin (R = 0.70; P < 0.0001). CONCLUSIONS: A significant correlation in this study between hair gadolinium concentrations and brain and skin gadolinium concentrations suggests that hair may serve as a safe and effective biomonitoring tissue for patients who receive GBCA injections.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype.

Magnetic resonance imaging and the female sexual response: overview of techniques, results, and future directions.

INTRODUCTION: Magnetic resonance imaging (MRI) is becoming a frequently used tool in the study of sexual physiology and neurophysiology. AIM: This report reviews various MRI methods used to study the female sexual arousal response. METHODS: Retrospective review of pertinent literature. RESULTS: Dynamic genital MRI studies enable the visualization of the physiologic arousal response that provides the direct observation of the time course and magnitude of this response, along with the variability that appears to occur in women with sexual arousal disorder. Functional brain MR studies are described and summarized along with an overview of what we have learned. Finally, the speculation on how we may be able to use MRI technology to better understand the female sexual response and to help in validating new drug treatments or in devising new treatment strategies for sexual dysfunction is also presented. CONCLUSIONS: Neuroimaging has already been proven as an invaluable research tool to study the sexual response in women both in the pelvis as well as within the brain. Using these techniques, major inroads are being made to improve the understanding of the sexual arousal process in women.

Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention.

OBJECT: The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. METHODS: Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (kappa > 0.4). CONCLUSIONS: Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.

Magnetic resonance imaging of SILCS diaphragm: anatomical considerations and corroboration with clinical fit.

BACKGROUND: We performed a pilot study to evaluate in vivo the fit of the new SILCS diaphragm, a single-size cervical barrier, using magnetic resonance imaging (MRI) in a group of women varying in body mass and parity. STUDY DESIGN: Two healthy premenopausal women were recruited for each of the following groups: body mass index (BMI)<25, BMI=25-30 and BMI>30. One woman in each group was nulliparous and one was multiparous. Subjects were instructed on the placement of the SILCS diaphragm. Each subject underwent three MRI scans: baseline, with the SILCS diaphragm in place and after placement of intravaginal contrast and simulated intercourse. RESULTS: The SILCS diaphragm was easily identified on MRI. In all subjects, the diaphragm covered the cervix. The position of the diaphragm did not change after simulated intercourse. The appropriate position of the diaphragm, as assessed by the subjects and the practitioner, was corroborated by the MR images. The intravaginal contrast was not readily visible on the images, precluding assessment of the diaphragm's barrier properties. CONCLUSION: MRI confirms the anatomic position of the SILCS diaphragm in vivo, among a sample of women varying in body mass and parity.