Purpose
Patients with steno-occlusive arterial disease may develop cerebral hypoperfusion with possible neurologic sequelae. The aim of the study is to verify the possible role of SWI, as a marker of ...cerebral hypoperfusion, in the identification of patient subgroups with significant chronic occlusions/stenoses at risk of critical cerebral hypoperfusion.
Methods
We retrospectively identified 37 asymptomatic patients with chronic intra-extracranial occlusion/stenosis of the anterior circulation from a prospective brain MRI register between 2016 and 2020. All patients underwent 3 Tesla MRI. The imaging protocol included the following: SWI, 3D-FLAIR, DWI sequences, and 3D-TOF MRA. SWI findings were graded for the presence of asymmetric intracranial cortical veins (grades 1 to 4). The presence of collateralization was assessed with concomitant multiphase-CTA. FLAIR was evaluated for the presence of distal hyperintense vessels (DHVs), a described marker of flow impairment, and possible collateralization. Cerebral blood flow and arterial transit artifacts (ATAs) were evaluated at pCASL in 29 patients.
Results
SWI showed multiple hypointense vessels (MHVs) in 22/37 patients in the cerebral hemisphere ipsilateral to vessel occlusion/stenosis. SWI-MHV grade 1 was found in 15 patients (40.5%), grade 2 in 18 patients (48.7%), and grade 3 in 3 patients (8.1%); in one patient, SWI was graded as 4 (2.7%). A significant relationship was found among MHV, DHV, collaterals, ATAs, and hypoperfused areas on pCASL and with patients’ previous neurological symptoms.
Conclusion
SWI-MVH correlates with chronic cerebral flow impairment and is related to hypoperfusion and collateralization. It may help identify a subgroup of patients benefitting from revascularization.
Purpose
Vessel wall imaging (VWI) with black-blood (BB) technique can demonstrate aneurysmal enhancement preluding to growth/rupture in treatment-naive cerebral aneurysms. Interestingly, recent works ...showed that BB enhancement may also occur in endovascularly treated aneurysms, though its meaning is controversial. Hypothesizing a flow-related mechanism of BB enhancement, we explored its relationship with incomplete occlusion status and coil packing density at DSA.
Methods
We analyzed the subjects undergoing 3T MRI between January 2017 and October 2020 for a previous aneurysmal coiling. All the MRI studies included pre- and post-contrast 3D BB sequences. The presence of intra-aneurysmal pre-contrast BB signal was assessed. BB enhancement (when present) was classified as follows: (1) enhancement at the neck, (2) intrasaccular/intra-coil enhancement, and (3) peripheral enhancement. Coil packing density and aneurysmal occlusion status (according to the modified Raymond-Roy classification, MRRC) were determined on post-treatment DSA and compared with BB findings using generalized linear mixed-effect model and ANOVA. Significant
p
values were <0.05.
Results
Forty-eight aneurysms from 44 patients were eligible for analysis. Pre-contrast BB signal was observed in 50% of the aneurysms and showed a relationship with baseline aneurysmal size. BB enhancement was detectable in 31 aneurysms (65%), being significantly associated with incomplete aneurysmal occlusion and reduced coil packing density at DSA.
Conclusion
BB enhancement of coiled aneurysms is related with increasing degrees of post-coiling aneurysmal remnants and with loose coil packing density at DSA. This supports a hemodynamic interpretation of BB enhancement in long-term coiled aneurysms.
The aim of this study was to determine a safe and effective dose of gadopiclenol, a new high relaxivity macrocyclic gadolinium-based contrast agent. Based on the contrast-to-noise ratio (CNR) as ...primary criterion, this new agent was compared with gadobenate dimeglumine in patients with contrast-enhancing central nervous system lesions.
This phase IIb international, multicenter, double-blind, randomized, controlled, parallel dose groups, and cross-over study included adult patients with known or highly suspected lesions with disrupted blood-brain barrier. Patients were randomized to 1 of 4 doses of gadopiclenol (0.025, 0.05, 0.1, 0.2 mmol/kg) and to 1 series of 2 magnetic resonance imaging scans: gadopiclenol then gadobenate dimeglumine at 0.1 mmol/kg or vice versa. The qualitative and quantitative efficacy evaluations were performed by 3 independent off-site blinded readers. Adverse events were monitored up to 1 day after second magnetic resonance imaging.
The study population included 272 patients (58.5% females) with a mean (SD) age of 53.8 (13.6) years. The superiority of gadopiclenol over gadobenate dimeglumine was statistically demonstrated at 0.2 and 0.1 mmol/kg for all readers with an increase in CNR of more than 30% (P ≤ 0.0007). At 0.05 mmol/kg, gadopiclenol showed a CNR of similar magnitude as gadobenate dimeglumine at 0.1 mmol/kg, with no statistically significant difference. Similar results were obtained for lesion-to-brain ratio and contrast enhancement percentage, as secondary criteria. The relationship between CNR and dose of gadopiclenol was linear for all readers. Mean scores for lesion visualization variables, particularly lesion contrast enhancement, tended to be higher with gadopiclenol at 0.1 and 0.2 mmol/kg compared with gadobenate dimeglumine. All 3 readers mainly expressed an overall diagnostic preference for images with gadopiclenol at 0.1 mmol/kg (45.3%, 50.9%, or 86.8% of images) or expressed no preference (49.1%, 49.1%, or 9.4%, respectively), whereas preference for images with gadobenate dimeglumine was reported by 2 readers for 3.8% and 5.7% of the images. Predominantly, no preference was expressed when comparing images with gadopiclenol at 0.05 mmol/kg to those with gadobenate dimeglumine.Rates of adverse reactions were comparable for gadopiclenol (11.7%) and gadobenate dimeglumine (12.1%). Changes from baseline of more than 25% in serum creatinine and estimated glomerular filtration rate occurred in less than 2% of patients equally for gadopiclenol and gadobenate dimeglumine. Changes from baseline for the values of blood urea nitrogen and cystatin C were also similar between gadopiclenol and gadobenate dimeglumine. No safety concerns were detected on centralized electrocardiography readings.
Between the doses of 0.025 and 0.2 mmol/kg of gadopiclenol, the increase in CNR is linear. Compared with gadobenate dimeglumine at 0.1 mmol/kg, the doses of 0.05 and 0.1 mmol/kg of gadopiclenol gave similar or significantly greater contrast enhancement, respectively, and thus both doses can be considered for future phase III studies.
Gadobutrol is a gadolinium (Gd)-based contrast agent for magnetic resonance imaging (MRI). In India, gadobutrol is approved for MRI of the central nervous system (CNS), liver, kidneys, breast and for ...MR angiography for patients 2 years and older. The standard dose for all age groups is 0.1 mmol/kg body weight. The safety profile has been demonstrated in 42 clinical phase 2 to 4 studies (>6800 patients), 7 observational studies, and by assessing pharmacovigilance data of 29 million applications. Furthermore, studies in children, adults, and elderly and in patients with impaired liver or kidney function did not show any increased adverse event rate. Diagnostic efficacy was demonstrated in numerous studies and various indications, such as diseases of the CNS, peripheral and supra-aortic vessels, kidneys, liver, and breast.
Summary
Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating ...sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut‐MYD88) and interleukin‐10 (IL‐10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra‐CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut‐MYD88 was assessed by TaqMan‐based polymerase chain reaction. IL‐6 and IL‐10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme‐linked immunosorbent assay. Mut‐MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue‐CSF samples. IL‐10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL‐6 transcripts was negligible. In CSF samples, mut‐MYD88 and high IL‐10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL‐6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL‐10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut‐MYD88 and IL‐10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related ...toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 μg/m2) afterward. This trial included 2 phases: an “explorative phase” addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid–single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an “expansion phase” with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.
•NGR-hTNF-α targets CD13+ tumor vessels and increases vascular permeability selectively in tumor/peritumoral areas of PCNSL.•R-CHOP preceded by low-dose NGR-hTNF was not associated with unexpected toxicity and resulted in tumor regression in 9 of 12 PCNSL patients.
Display omitted
PDF
