MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma.

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS).

In sialendoscopy, ducts are dilated and the salivary glands are irrigated with saline. Contrast-enhanced ultrasound sialendoscopy (CEUSS), using microbubbles, may facilitate the monitoring of irrigation solution penetration in the ductal system and parenchyma. It is imperative to test CEUSS for its safety and feasibility in Sjögren's syndrome (SS) patients. CEUSS was performed on 10 SS patients. The primary outcomes were safety, determined by the occurrence of (serious) adverse events ((S)AEs), and feasibility. The secondary outcomes were unstimulated and stimulated whole saliva (UWS and SWS) flow rates, xerostomia inventory (XI), clinical oral dryness score, pain, EULAR Sjögren's syndrome patient reported index (ESSPRI), and gland topographical alterations. CEUSS was technically feasible in all patients. Neither SAEs nor systemic reactions related to the procedure were observed. The main AEs were postoperative pain (two patients) and swelling (two patients). Eight weeks after CEUSS, the median UWS and SWS flow had increased significantly from 0.10 to 0.22 mL/min (p = 0.028) and 0.41 to 0.61 mL/min (p = 0.047), respectively. Sixteen weeks after CEUSS, the mean XI was reduced from 45.2 to 34.2 (p = 0.02). We conclude that CEUSS is a safe and feasible treatment for SS patients. It has the potential to increase salivary secretion and reduce xerostomia, but this needs further investigation.

Continuing Challenges in the Definitive Diagnosis of Cushing's Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up.

The definitive diagnosis of Cushing's disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing's syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. 11C-Met showed higher pituitary adenoma detection than 18F-FDG PET-CT (87% versus 49%). Up to 100% detection rates were found for 18F-FET, 68Ga-DOTA-TATE, and 68Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS.

Brain miliary enhancement.

PURPOSE: Miliary enhancement refers to the presence of multiple small, monomorphic, enhancing foci on T1-weighted post-contrast MRI images. In the absence of a clear clinical presentation, a broad differential diagnosis may result in invasive procedures and possibly brain biopsy for diagnostic purposes. METHODS: An extensive review of the literature is provided for diseases that may present with miliary enhancement on T1-weighted brain MR images. Additional disease-specific findings, both clinical and radiological, are summarized and categorized by the presence or absence of perivascular space involvement. RESULTS: Miliary pattern of enhancement may be due to a variety of underlying causes, including inflammatory, infectious, nutritional or neoplastic processes. The recognition of disease spread along the perivascular spaces in addition to the detection or exclusion of disease-specific features on MRI images, such as leptomeningeal enhancement, presence of haemorrhagic lesions, spinal cord involvement and specific localisation or systemic involvement, allows to narrow the potential differential diagnoses. CONCLUSION: A systematic approach to disease-specific findings from both clinical and radiological perspectives might facilitate diagnostic work-up, and recognition of disease spread along the perivascular spaces may help narrowing down differential diagnoses and may help to minimize the use of invasive diagnostic procedures.

Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke: 24-Hour Versus 1-Week Imaging.

BACKGROUND AND PURPOSE: Ischemic lesion volume (ILV) on noncontrast computed tomography at 1 week can be used as a secondary outcome measure in patients with acute ischemic stroke. Twenty-four-hour ILV on noncontrast computed tomography has greater availability and potentially allows earlier estimation of functional outcome. We aimed to assess lesion growth 24 hours after stroke onset and compare the associations of 24-hour and 1-week ILV with functional outcome. METHODS: We included 228 patients from MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), who received noncontrast computed tomography at 24-hour and 1-week follow-up on which ILV was measured. Relative and absolute lesion growth was determined. Logistic regression models were constructed either including the 24-hour or including the 1-week ILV. Ordinal and dichotomous (0-2 and 3-6) modified Rankin scale scores were, respectively, used as primary and secondary outcome measures. RESULTS: Median ILV was 42 mL (interquartile range, 21-95 mL) and 64 mL (interquartile range: 30-120 mL) at 24 hours and 1 week, respectively. Relative lesion growth exceeding 30% occurred in 121 patients (53%) and absolute lesion growth exceeding 20 mL occurred in 83 patients (36%). Both the 24-hour and 1-week ILVs were similarly significantly associated with functional outcome (both P<0.001). In the logistic analyses, the areas under the curve of the receiver-operator characteristic curves were similar: 0.85 (95% confidence interval, 0.80-0.90) and 0.87 (95% confidence interval, 0.82-0.91) for including the 24-hour and 1-week ILV, respectively. CONCLUSIONS: Growth of ILV is common 24-hour poststroke onset. Nevertheless, the 24-hour ILV proved to be a valuable secondary outcome measure as it is equally strongly associated with functional outcome as the 1-week ILV. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.

Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. METHODS: For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ2 test to assess treatment effect modification by CBS. RESULTS: Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04-1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12-2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. CONCLUSIONS: A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR1804. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.

Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN).

BACKGROUND: Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged ≥18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0-4 (large infarct) versus 5-7 (moderate infarct) versus 8-10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. FINDINGS: 496 patients-232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group-were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8-10: ASPECTS 0-4: 0·79 [95% CI 0·20-3·19], p=0·740; and ASPECTS 5-7: 1·02 [0·44-2·35], p=0·966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0-4: eight [73%] of 11 patients in treatment and usual care group vs 11 [58%] of 19 in usual care alone group, p=0·42; ASPECTS 5-7: 32 [59%] of 54 vs 19 [49%] of 39, p=0·31; ASPECTS 8-10: 70 [42%] of 167 vs 82 [40%] of 206; p=0·68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8-10 subgroup (eight [5%] vs one [<1%]; p=0·007). INTERPRETATION: Contrary to findings from previous studies suggesting that only patients with non-contrast CT ASPECTS of more than 7 benefit from intra-arterial treatment, data from this study suggest that patients with ASPECTS 5-7 should be treated. Further evidence is needed for patients with ASPECTS 0-4, for whom treatment might yield only marginal absolute benefit. FUNDING: Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, Medac/Lamepro, Penumbra, Stryker, and Top Medical.

Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. RESULTS: We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7-6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0-2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7-2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1-8.7] for patients with absent collaterals (grade 0). CONCLUSIONS: In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke.

INTRODUCTION: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. METHODS: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R (2) was assessed to determine the additional value of CTA and CTP. RESULTS: At follow-up, 612 patients (67.5%) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8-69.6). Regarding infarct presence, the AUC of 0.82 (95% confidence interval (CI) 0.79-0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95% CI 0.82-0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R (2) = 0.58) was superior to patient characteristics and non-contrast CT alone (R (2) = 0.44) and to addition of CTA alone (R (2) = 0.55) or CTP alone (R (2) = 0.54; all p < 0.001). CONCLUSION: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment.