To prospectively investigate chemical exchange saturation transfer (CEST) MRI in glioblastoma patients as predictor of early tumor progression after first-line treatment.
Twenty previously untreated ...glioblastoma patients underwent CEST MRI employing a 7T whole-body scanner. Nuclear Overhauser effect (NOE) as well as amide proton transfer (APT) CEST signals were isolated using Lorentzian difference (LD) analysis and relaxation compensated by the apparent exchange-dependent relaxation rate (AREX) evaluation. Additionally, NOE-weighted asymmetric magnetic transfer ratio (MTRasym) and downfield-NOE-suppressed APT (dns-APT) were calculated. Patient response to consecutive treatment was determined according to the RANO criteria. Mean signal intensities of each contrast in the whole tumor area were compared between early-progressive and stable disease.
Pre-treatment tumor signal intensity differed significantly regarding responsiveness to first-line therapy in NOE-LD (
= 0.0001), NOE-weighted MTRasym (
= 0.0186) and dns-APT (
= 0.0328) contrasts. Hence, significant prediction of early progression was possible employing NOE-LD (AUC = 0.98,
= 0.0005), NOE-weighted MTRasym (AUC = 0.83,
= 0.0166) and dns-APT (AUC = 0.80,
= 0.0318). The NOE-LD provided the highest sensitivity (91%) and specificity (100%).
CEST derived contrasts, particularly NOE-weighted imaging and dns-APT, yielded significant predictors of early progression after fist-line therapy in glioblastoma. Therefore, CEST MRI might be considered as non-invasive tool for customization of treatment in the future.
Abstract
Background
No systemic treatment has been established for meningioma progressing after local therapies.
Methods
This randomized, multicenter, open-label, phase II study included adult ...patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses.
Results
Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio HR = 1.42; 80% CI, 1.00-2.03; P = .294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P = .94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS.
Conclusions
Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.
Sciatic nerve palsy related to hip replacement surgery (HRS) is among the most common causes of sciatic neuropathies. The sciatic nerve may be injured by various different periprocedural mechanisms. ...The precise localization and extension of the nerve lesion, the determination of nerve continuity, lesion severity, and fascicular lesion distribution are essential for assessing the potential of spontaneous recovery and thereby avoiding delayed or inappropriate therapy. Adequate therapy is in many cases limited to conservative management, but in certain cases early surgical exploration and release of the nerve is indicated. Nerve-conduction-studies and electromyography are essential in the diagnosis of nerve injuries. In postsurgical nerve injuries, additional diagnostic imaging is important as well, in particular to detect or rule out direct mechanical compromise. Especially in the presence of metallic implants, commonly applied diagnostic imaging tests generally fail to adequately visualize nervous tissue. MRI has been deemed problematic due to implant-related artifacts after HRS. In this study, we describe for the first time the spectrum of imaging findings of Magnetic Resonance neurography (MRN) employing pulse sequences relatively insensitive to susceptibility artifacts (susceptibility insensitive MRN, siMRN) in a series of 9 patients with HRS procedure related sciatic nerve palsy. We were able to determine the localization and fascicular distribution of the sciatic nerve lesion in all 9 patients, which clearly showed on imaging predominant involvement of the peroneal more than the tibial division of the sciatic nerve. In 2 patients siMRN revealed direct mechanical compromise of the nerve by surgical material, and in one of these cases indication for surgical release of the sciatic nerve was based on siMRN. Thus, in selected cases of HRS related neuropathies, especially when surgical exploration of the nerve is considered, siMRN, with its potential to largely overcome implant related artifacts, is a useful diagnostic addition to nerve-conduction-studies and electromyography.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several studies have analyzed a correlation between the apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI and the tumor cellularity of corresponding histopathological specimens ...in brain tumors with inconclusive findings. Here, we compared a large dataset of ADC and cellularity values of stereotactic biopsies of glioblastoma patients using a new postprocessing approach including trajectory analysis and automatic nuclei counting.
Thirty-seven patients with newly diagnosed glioblastomas were enrolled in this study. ADC maps were acquired preoperatively at 3T and coregistered to the intraoperative MRI that contained the coordinates of the biopsy trajectory. 561 biopsy specimens were obtained; corresponding cellularity was calculated by semi-automatic nuclei counting and correlated to the respective preoperative ADC values along the stereotactic biopsy trajectory which included areas of T1-contrast-enhancement and necrosis.
There was a weak to moderate inverse correlation between ADC and cellularity in glioblastomas that varied depending on the approach towards statistical analysis: for mean values per patient, Spearman's ρ = -0.48 (p = 0.002), for all trajectory values in one joint analysis Spearman's ρ = -0.32 (p < 0.001). The inverse correlation was additionally verified by a linear mixed model.
Our data confirms a previously reported inverse correlation between ADC and tumor cellularity. However, the correlation in the current article is weaker than the pooled correlation of comparable previous studies. Hence, besides cell density, other factors, such as necrosis and edema might influence ADC values in glioblastomas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glioblastoma multiforme alters healthy tissue vasculature by inducing angiogenesis and vascular remodeling. To fully comprehend the structural and functional properties of the resulting vascular ...network, it needs to be studied collectively by considering both geometric and topological properties. Utilizing Single Plane Illumination Microscopy (SPIM), the detailed capillary structure in entire healthy and tumor-bearing mouse brains could be resolved in three dimensions. At the scale of the smallest capillaries, the entire vascular systems of bulk U87- and GL261-glioblastoma xenografts, their respective cores, and healthy brain hemispheres were modeled as complex networks and quantified with fundamental topological measures. All individual vessel segments were further quantified geometrically and modular clusters were uncovered and characterized as meta-networks, facilitating an analysis of large-scale connectivity. An inclusive comparison of large tissue sections revealed that geometric properties of individual vessels were altered in glioblastoma in a relatively subtle way, with high intra- and inter-tumor heterogeneity, compared to the impact on the vessel connectivity. A network topology analysis revealed a clear decomposition of large modular structures and hierarchical network organization, while preserving most fundamental topological classifications, in both tumor models with distinct growth patterns. These results augment our understanding of cerebrovascular networks and offer a topological assessment of glioma-induced vascular remodeling. The findings may help understand the emergence of hypoxia and necrosis, and prove valuable for therapeutic interventions such as radiation or antiangiogenic therapy.
MRI is used for screening, initial diagnosis and follow-up of brain metastases. Multiparametric MRI protocols encompass an array of image sequences to depict key aspects of metastases morphology and ...biology. Given the recent safety concerns of Gd-administration and the retention of linear Gd-agents in the brain, non-contrast sequences are currently evaluated regarding their diagnostic value for brain imaging studies. Susceptibility weighted imaging has been established as a valuable clinical and research tool that is heavily used in clinical practice and utilized in diverse pathologies ranging from neuroinflammation, neurovascular disease to neurooncology. We review the value of SWI in the field of brain metastases with an emphasis on its role in early diagnosis, determination of the primary tumor entity, treatment monitoring and discuss therapy-associated changes that can affect SWI. We also review recent insights on the role of "isolated SWI signals" and the controversy on the specificity of SWI for the early detection of brain metastases.
To investigate the influence of cerebral atrophy on clinical outcome in patients with supratentorial intracerebral hemorrhage.
Computed tomography scans of 320 patients included in a prospective, ...multicenter trial were used for a segmentation analysis to determine the supratentorial cerebral volume. A logistic regression analysis was used to explore its effect on outcome after 90 days in addition to other clinical and imaging parameters.
Cerebral volume loss significantly reduced the odds for favorable outcome after 90 days (odds ratio=0.91; confidence interval, 0.85-0.99; P=0.02).
Cerebral atrophy is an independent predictor of unfavorable outcome after intracerebral hemorrhage, indicating reduced functional recovery potential in these individuals.
Nerve damage in diabetic neuropathy (DN) is assumed to begin in the distal legs with a subsequent progression to hands and arms at later stages. In contrast, recent studies have found that lower limb ...nerve lesions in DN predominate at the proximal sciatic nerve and that, in the upper limb, nerve functions can be impaired at early stages of DN.
In this prospective, single-center cross-sectional study, participants underwent diffusion-weighted 3 Tesla magnetic resonance neurography in order to calculate the sciatic nerve's fractional anisotropy (FA), a surrogate parameter for structural nerve integrity. Results were correlated with clinical and electrophysiological assessments of the lower limb and an examination of hand function derived from the Purdue Pegboard Test.
Overall, 71 patients with diabetes, 11 patients with prediabetes and 25 age-matched control subjects took part in this study. In patients with diabetes, the sciatic nerve's FA showed positive correlations with tibial and peroneal nerve conduction velocities (
= 0.62;
< 0.001 and
= 0.56;
< 0.001, respectively), and tibial and peroneal nerve compound motor action potentials (
= 0.62;
< 0.001 and
= 0.63;
< 0.001, respectively). Moreover, the sciatic nerve's FA was correlated with the Pegboard Test results in patients with diabetes (
= 0.52;
< 0.001), prediabetes (
= 0.76;
< 0.001) and in controls (
= 0.79;
= 0.007).
This study is the first to show that the sciatic nerve's FA is a surrogate marker for functional and electrophysiological parameters of both upper and lower limbs in patients with diabetes and prediabetes, suggesting that nerve damage in these patients is not restricted to the level of the symptomatic limbs but rather affects the entire peripheral nervous system.
Purpose
Diabetes is associated with vascular dysfunction potentially impairing collateral recruitment in acute ischemic stroke. This retrospective study aimed at analyzing the impact of diabetes on ...collateralization assessed on dynamic CTA.
Methods
Collaterals were retrospectively assessed on CT perfusion–derived dynamic CTA according to the mCTA score by Menon in a cohort of patients with an acute occlusion of the M1 segment or carotid T. The extent of collateral circulation was related to the history of diabetes and to admission blood glucose and HbA1c levels.
Results
Two hundred thirty-nine patients were included. The mCTA collateral score was similar in patients with diabetes (median 3, interquartile range 3–4) and without diabetes (median 4, interquartile range 3–4) (
P
= 0.823). Diabetes was similarly frequent in patients with good (18.8%), intermediate (16.1%), and poor collaterals (16.0%) (
P
= 0.355). HbA1c was non-significantly higher in patients with poor collaterals (6.3 ± 1.5) compared to patients with intermediate (6.0 ± 0.9) and good collaterals (5.8 ± 0.9) (
P
= 0.061). Blood glucose levels were significantly higher in patients with poor compared to good collaterals (mean 141.6 vs. 121.8 mg/dl,
P
= 0.045). However, there was no significant difference between good and intermediate collaterals (mean 121.8 vs. 129.5 mg/dl,
P
= 0.161) as well as between intermediate and poor collaterals (129.5 vs. 141.6 mg/dl,
P
= 0.161).
Conclusion
There was no statistically significant difference among patients with good, intermediate, and poor collaterals regarding the presence of diabetes or HbA1c level on admission. However, stroke patients with poor collaterals tend to have higher blood glucose and HbA1c levels.
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