Robert J. McDonald

Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging

PURPOSE To determine if repeated intravenous exposures to gadolinium-based contrast agents (GBCAs) are associated with neuronal tissue deposition. MATERIALS AND METHODS In this institutional review board-approved single-center study, signal intensities from T1-weighted magnetic resonance (MR) images and postmortem neuronal tissue samples from 13 patients who underwent at least four GBCA-enhanced brain MR examinations between 2000 and 2014 (contrast group) were compared with those from 10 patients who did not receive GBCA (control group). Antemortem consent was obtained from all study participants. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus of these 23 deceased patients were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Associations between cumulative gadolinium dose, changes in T1-weighted MR signal intensity, and ICP-MS-derived tissue gadolinium concentrations were examined by using the Spearman rank correlation coefficient (ρ). RESULTS Compared with neuronal tissues of control patients, all of which demonstrated undetectable levels of gadolinium, neuronal tissues of patients from the contrast group contained 0.1-58.8 μg gadolinium per gram of tissue, in a significant dose-dependent relationship that correlated with signal intensity changes on precontrast T1-weighted MR images (ρ = 0.49-0.93). All patients in the contrast group had relatively normal renal function at the time of MR examination. Gadolinium deposition in the capillary endothelium and neural interstitium was observed only in the contrast group. CONCLUSION Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.

Intravenous Contrast Material–induced Nephropathy: Causal or Coincident Phenomenon?

PURPOSE To determine the causal association and effect of intravenous iodinated contrast material exposure on the incidence of acute kidney injury (AKI), also known as contrast material-induced nephropathy (CIN). MATERIALS AND METHODS This retrospective study was approved by an institutional review board and was HIPAA compliant. Informed consent was waived. All contrast material-enhanced (contrast group) and unenhanced (noncontrast group) abdominal, pelvic, and thoracic CT scans from 2000 to 2010 were identified at a single facility. Scan recipients were sorted into low- (<1.5 mg/dL), medium- (1.5-2.0 mg/dL), and high-risk (>2.0 mg/dL) subgroups of presumed risk for CIN by using baseline serum creatinine (SCr) level. The incidence of AKI (SCr ≥ 0.5 mg/dL above baseline) was compared between contrast and noncontrast groups after propensity score adjustment by stratification, 1:1 matching, inverse weighting, and weighting by the odds methods to reduce intergroup selection bias. Counterfactual analysis was used to evaluate the causal relation between contrast material exposure and AKI by evaluating patients who underwent contrast-enhanced and unenhanced CT scans during the study period with the McNemar test. RESULTS A total of 157,140 scans among 53,439 unique patients associated with 1,510,001 SCr values were identified. AKI risk was not significantly different between contrast and noncontrast groups in any risk subgroup after propensity score adjustment by using reported risk factors of CIN (low risk: odds ratio [OR], 0.93; 95% confidence interval [CI]: 0.76, 1.13; P = .47; medium risk: odds ratio, 0.97; 95% CI: 0.81, 1.16; P = .76; high risk: OR, 0.91; 95% CI: 0.66, 1.24; P = .58). Counterfactual analysis revealed no significant difference in AKI incidence between enhanced and unenhanced CT scans in the same patient (McNemar test: χ(2) = 0.63, P = .43) (OR = 0.92; 95% CI: 0.75, 1.13; P = .46). CONCLUSION Following adjustment for presumed risk factors, the incidence of CIN was not significantly different from contrast material-independent AKI. These two phenomena were clinically indistinguishable with established SCr-defined criteria, suggesting that intravenous iodinated contrast media may not be the causative agent in diminished renal function after contrast material administration. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121823/-/DC1.

Frequency of Acute Kidney Injury Following Intravenous Contrast Medium Administration: A Systematic Review and Meta-Analysis

PURPOSE To perform a systematic review and meta-analysis of controlled studies examining the incidence of acute kidney injury (AKI) and other outcomes in patients exposed to intravenous (i.v.) contrast medium compared with patients who underwent an imaging examination without contrast medium or were otherwise unexposed (control group). MATERIALS AND METHODS MEDLINE, EMBASE, Scopus, and the Cochrane Library were searched for all articles published through September 2011 that contained search terms related to nephrotoxicity following intravenous contrast medium administration. Two independent reviewers identified studies in which the incidence of AKI in patients exposed to i.v. contrast medium was directly compared with the incidence of AKI in unexposed patients through analysis of changes in serum creatinine level or estimated glomerular filtration rate 48-72 hours following imaging procedures or admission. Study characteristics and outcomes of AKI, dialysis, and mortality were extracted by using a standardized protocol. Relative risk (RR) was calculated by using random-effects models and was tested in subgroups of different patient comorbidities, contrast medium types, and AKI diagnostic criteria. RR results of less than 1.00 indicated that there was a higher incidence of these outcomes in the group that did not receive contrast medium (non-contrast medium group). RESULTS Of the 1489 studies originally identified, 13 nonrandomized studies (0.9%) representing 25,950 patients met inclusion criteria. In the group that received contrast medium (contrast medium group), risk of AKI (RR = 0.79; 95% confidence interval [CI]: 0.62, 1.02; P = .07), death (RR = 0.95; 95% CI: 0.55, 1.67; P = .87), and dialysis (RR = 0.88; 95% CI: 0.23, 3.43; P = .85) was similar, compared with the risk of AKI in the non-contrast medium group. This pattern was observed regardless of i.v. contrast medium type, diagnostic criteria for AKI, or whether patients had diabetes mellitus or renal insufficiency. CONCLUSION Controlled contrast medium-induced nephropathy studies demonstrate a similar incidence of AKI, dialysis, and death between the contrast medium group and control group. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121460/-/DC1.

Hsp90 Inhibition Depletes Chk1 and Sensitizes Tumor Cells to Replication Stress

DNA damage and replication stress activate the Chk1 signaling pathway, which blocks S phase progression, stabilizes stalled replication forks, and participates in G2 arrest. In this study, we show that Chk1 interacts with Hsp90, a molecular chaperone that participates in the folding, assembly, maturation, and stabilization of specific proteins known as clients. Consistent with Chk1 being an Hsp90 client, we also found that Chk1 but not Chk2 is destabilized in cells treated with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG-mediated Chk1 loss blocked the ability of Chk1 to target Cdc25A for proteolytic destruction, demonstrating that the Chk1 signaling pathway was disrupted in the 17-AAG-treated cells. Finally, 17-AAG-mediated disruption of Chk1 activation dramatically sensitized various tumor cells to gemcitabine, an S phase-active chemotherapeutic agent. Collectively, our studies identify Chk1 as a novel Hsp90 client and suggest that pharmacologic inhibition of Hsp90 may sensitize tumor cells to chemotherapeutic agents by disrupting Chk1 function during replication stress.

Risk of Intravenous Contrast Material–mediated Acute Kidney Injury: A Propensity Score–matched Study Stratified by Baseline-estimated Glomerular Filtration Rate

PURPOSE To determine the effect of baseline estimated glomerular filtration rate (eGFR) on the causal association between intravenous iodinated contrast material exposure and subsequent development of acute kidney injury (AKI) in propensity score-matched groups of patients who underwent contrast material-enhanced or unenhanced computed tomography (CT). MATERIALS AND METHODS This retrospective study was HIPAA compliant and institutional review board approved. All patients who underwent contrast-enhanced (contrast material group) or unenhanced (non-contrast material group) CT between 2000 and 2010 were identified and stratified according to baseline eGFR by using Kidney Disease Outcomes Quality Initiative cutoffs for chronic kidney disease into subgroups with eGFR of 90 or greater, 60-89, 30-59, and less than 30 mL/min/1.73 m(2). Propensity score generation and 1:1 matching of patients were performed in each eGFR subgroup. Incidence of AKI (serum creatinine [SCr] increase of ≥0.5 mg/dL [≥44.2 μmol/L] above baseline) was compared in the matched subgroups by using the Fisher exact test. RESULTS A total of 12 508 propensity score-matched patients with contrast-enhanced and unenhanced scans met all inclusion criteria. In this predominantly inpatient cohort, the incidence of AKI significantly increased with decreasing baseline eGFR (P < .0001). However, this incidence was not significantly different between contrast material and non-contrast material groups in any eGFR subgroup; for the subgroup with eGFR of 90 or greater (n = 1642), odds ratio (OR) was 0.91 (95% confidence interval [CI]: 0.38, 2.15), P = .82; for the subgroup with eGFR of 60-89 (n = 3870), OR was 1.03 (95% CI: 0.66, 1.60), P = .99; for the subgroup with eGFR of 30-59 (n = 5510), OR was 0.94 (95% CI: 0.76, 1.18), P = .65; and for the subgroup with eGFR of less than 30 mL/min/1.73 m(2) (n = 1486), OR was 0.97 (95% CI: 0.72, 1.30), P = .89. CONCLUSION Diminished eGFR is associated with an increased risk of SCr-defined AKI following CT examinations. However, the risk of AKI is independent of contrast material exposure, even in patients with eGFR of less than 30 mL/min/1.73 m(2).

Vertebroplasty in Multiple Myeloma: Outcomes in a Large Patient Series

BACKGROUND AND PURPOSE: Despite the literature supporting the efficacy of vertebroplasty for treatment of osteoporotic vertebral compression fractures, few reports exist documenting its use in the treatment of compression fractures in multiple myeloma patients. Accordingly, we sought to characterize the imaging characteristics, clinical course, and outcomes in myeloma patients treated with vertebroplasty. MATERIALS AND METHODS: We performed a retrospective review of clinical outcome data from 67 multiple myeloma patients treated with vertebroplasty since October 2000. Quantitative outcome data including the Roland Morris Disability Questionnaire (RDQ) and Visual Analog Scales for pain and qualitative outcome data (self-reported pain, mobility, and narcotic use) were collected preoperatively, immediately after vertebroplasty, and at 1 week, 1 month, 6 months, and 1 year after treatment. RESULTS: Significant improvements in all of the outcome measures were observed postoperatively and throughout the duration of follow-up. Quantitative outcome measures (RDQ, analog pain scale 0–10, with rest and activity) improved by 11.0 (48%; P < .0001), 2.7 (25%; P < .001), and 5.3 (48%; P < .0001) points, respectively, with persistent improvement at 1 year (P < .01; P < .03; P < .001). Eighty-two percent and 89% of patients experienced a significant improvement in subjective rest pain and activity pain, respectively. Subjective scores achieved durable improvements, with 65% of patients requiring fewer narcotics after vertebroplasty and 70% having improved mobility. CONCLUSION: Vertebroplasty provides significant and durable pain relief for patients with intractable spinal pain secondary to compression fractures resulting from multiple myeloma.

Intravenous Contrast Material Exposure Is Not an Independent Risk Factor for Dialysis or Mortality

PURPOSE To determine the risk of emergent dialysis and short-term mortality following intravenous iodinated contrast material exposure. MATERIALS AND METHODS This single-center retrospective study was HIPAA compliant and institutional review board approved. All contrast material-enhanced (contrast group) and unenhanced (noncontrast group) abdominal, pelvic, and thoracic computed tomography scans from 2000-2010 were identified. Patients in the contrast and noncontrast groups were compared following propensity score-based 1:1 matching to reduce intergroup selection bias. Patients with preexisting diabetes mellitus, congestive heart failure, or chronic or acute renal failure were identified as high-risk patient subgroups for nephrotoxicity. The effects of contrast material exposure on the rate of acute kidney injury ( AKI acute kidney injury ) (serum creatinine level ≥ 0.5 mg/dL [44.2 μmol/L] above baseline within 24-72 hours of exposure) and dialysis or death within 30 days of exposure were determined by using odds ratios ( OR odds ratio s) and covariate-adjusted Cox proportional hazards models. Results were validated with a bootstrapped sensitivity analysis. RESULTS The 1:1 matching on the basis of the propensity score yielded a cohort of 21 346 patients (10 673 in the contrast group, 10 673 in the noncontrast group). Within this cohort, the risks of AKI acute kidney injury ( OR odds ratio , 0.94; 95% confidence interval [ CI confidence interval ]: 0.83, 1.07; P = .38), emergent dialysis ( OR odds ratio , 0.96; 95% CI confidence interval : 0.54, 1.60; P = .89), and 30-day mortality (hazard ratio [ HR hazard ratio ], 0.97; 95% CI confidence interval : 0.87, 1.06; P = .45) were not significantly different between the contrast group and the noncontrast group. Although patients who developed AKI acute kidney injury had higher rates of dialysis and mortality, contrast material exposure was not an independent risk factor for either outcome for dialysis ( OR odds ratio , 0.89; 95% CI confidence interval : 0.40, 2.01; P = .78) or for mortality ( HR hazard ratio , 1.03; 95% CI confidence interval : 0.82, 1.32; P = .63), even among patients with compromised renal function or predisposing comorbidities. CONCLUSION Intravenous contrast material administration was not associated with excess risk of AKI acute kidney injury , dialysis, or death, even among patients with comorbidities reported to predispose them to nephrotoxicity.

Comparative Effectiveness of Unruptured Cerebral Aneurysm Therapies: Propensity Score Analysis of Clipping Versus Coiling

Background and Purpose— Endovascular therapy has increasingly become the most common treatment for unruptured cerebral aneurysms in the United States. We evaluated a national, multi-hospital database to examine recent utilization trends and compare periprocedural outcomes between clipping and coiling treatments of unruptured aneurysms. Methods— The Premier Perspective database was used to identify patients hospitalized between 2006 to 2011 for unruptured cerebral aneurysm who underwent clipping or coiling therapy. A logistic propensity score was generated for each patient using relevant patient, procedure, and hospital variables, representing the probability of receiving clipping. Covariate balance was assessed using conditional logistic regression. Following propensity score adjustment using 1:1 matching methods, the risk of in-hospital mortality and morbidity was compared between clipping and coiling cohorts. Results— A total of 4899 unruptured aneurysm patients (1388 clipping, 3551 coiling) treated at 120 hospitals were identified. Following propensity score adjustment, clipping patients had a similar likelihood of in-hospital mortality (odds ratio [OR], 1.43; 95% confidence interval [CI], 0.49–4.44; P=0.47) but a significantly higher likelihood of unfavorable outcomes, including discharge to long-term care (OR, 4.78; 95% CI, 3.51–6.58; P<0.0001), ischemic complications (OR, 3.42; 95% CI, 2.39–4.99; P<0.0001), hemorrhagic complications (OR, 2.16; 95% CI, 1.33–3.57; P<0.0001), postoperative neurological complications (OR, 3.39; 95% CI, 2.25–5.22; P<0.0001), and ventriculostomy (OR, 2.10; 95% CI, 1.01–4.61; P=0.0320) compared with coiling patients. Conclusions— Among patients treated for unruptured intracranial aneurysms in a large sample of hospitals in the United States, clipping was associated with similar mortality risk but significantly higher periprocedural morbidity risk compared with coiling.

Is the h-index Predictive of Greater NIH Funding Success Among Academic Radiologists?

RATIONALE AND OBJECTIVES Despite rapid adoption of the Hirsch index (h-index) as a measure of academic success, the correlations between the h-index and other metrics of productivity remain poorly understood. The aims of this study were to determine whether h-indices were associated with greater National Institutes of Health (NIH) funding success among academic radiologists. MATERIALS AND METHODS Using the Scopus database, h-indices were calculated for a random sample of academic radiologists with the rank of professor. Using the NIH tool Research Portfolio Online Reporting Tools Expenditures and Reports, we determined the number, classification, and total years of NIH grant funding as principal investigator for each radiologist. Differences in h-index, sorted by funding status, were determined using Wilcoxons tests. Associations between h-index and funding status were determined using logistic regression. Significant correlations between h-index and grant metrics were determined using Spearmans ρ. RESULTS Among 210 professors of radiology, 48 (23%) secured at least one NIH grant. The mean h-index was significantly higher among individuals who secured at least one NIH grant (19.1) compared to those who did not (10.4) (P < .0001). Professors with h-indices < 10 compared to those with h-indices > 10 were significantly less likely to receive NIH funding (odds ratio, 0.07; P = .0321). However, h-indices > 10 were not significantly predictive of greater funding. No significant relationships were observed between h-index and the number of grant awards, years of prior funding, the amounts of grant awards, or grant classification. CONCLUSION Having obtained at least one NIH grant was associated with a higher h-index, yet multiple or large grants, such as those for program projects, were not predictive of higher h-indices.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m2) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety.