To determine whether serum neurofilament light (NfL) correlates with CSF NfL, traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of ...traumatic axonal injury (TAI).
Participants were prospectively enrolled in Sweden and the United States between 2011 and 2019. The Swedish cohort included 45 hockey players with acute concussion sampled at 6 days, 31 with repetitive concussion with persistent postconcussive symptoms (PCS) assessed with paired CSF and serum (median 1.3 years after concussion), 28 preseason controls, and 14 nonathletic controls. Our second cohort included 230 clinic-based participants (162 with TBI and 68 controls). Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury.
In athletes with paired specimens, CSF NfL and serum NfL were correlated (
= 0.71,
0.0001). CSF and serum NfL distinguished players with PCS >1 year from PCS ≤1 year (area under the receiver operating characteristic curve AUROC 0.81 and 0.80). The AUROC for PCS >1 year vs preseason controls was 0.97. In the clinic-based cohort, NfL at enrollment distinguished patients with mild from those with moderate and severe TBI (
0.001 and
0.048). Serum NfL decreased over the course of 5 years (ß = -0.09 log pg/mL,
0.0001) but remained significantly elevated compared to controls. Serum NfL correlated with measures of functional outcome, MRI brain atrophy, and DTI estimates of TAI.
Serum NfL shows promise as a biomarker for acute and repetitive sports-related concussion and patients with subacute and chronic TBI.
This study provides Class III evidence that increased concentrations of NfL distinguish patients with TBI from controls.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have ...previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active ...in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved complete remission with DA-TEDDi-R. Increased aspergillosis was observed with ibrutinib monotherapy and DA-TEDDi-R. Aspergillosis was linked to BTK-dependent fungal immunity in a murine model. PCNSL is highly dependent on BCR signaling, and ibrutinib appears to enhance the efficacy of chemotherapy.
•Ibrutinib reduced tumor masses in 94% of patients with primary brain lymphoma•Chronic active B cell receptor signaling is a feature of primary brain lymphoma•Ibrutinib promotes fungal infections with Aspergillus fumigatus•TEDDi-R treatment produced durable remissions in refractory primary brain lymphoma
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor signaling. In a phase 1b study, Lionakis et al. observe promising therapeutic effects of the BTK inhibitor ibrutinib in PCNSL but also increased aspergillosis, which they show is linked to BTK-dependent fungal immunity in a mouse model.
Automatic skull-stripping or brain extraction of magnetic resonance (MR) images is often a fundamental step in many neuroimage processing pipelines. The accuracy of subsequent image processing relies ...on the accuracy of the skull-stripping. Although many automated stripping methods have been proposed in the past, it is still an active area of research particularly in the context of brain pathology. Most stripping methods are validated on T1-w MR images of normal brains, especially because high resolution T1-w sequences are widely acquired and ground truth manual brain mask segmentations are publicly available for normal brains. However, different MR acquisition protocols can provide complementary information about the brain tissues, which can be exploited for better distinction between brain, cerebrospinal fluid, and unwanted tissues such as skull, dura, marrow, or fat. This is especially true in the presence of pathology, where hemorrhages or other types of lesions can have similar intensities as skull in a T1-w image. In this paper, we propose a sparse patch based Multi-cONtrast brain STRipping method (MONSTR),22http://www.nitrc.org/projects/monstr. where non-local patch information from one or more atlases, which contain multiple MR sequences and reference delineations of brain masks, are combined to generate a target brain mask.
We compared MONSTR with four state-of-the-art, publicly available methods: BEaST, SPECTRE, ROBEX, and OptiBET. We evaluated the performance of these methods on 6 datasets consisting of both healthy subjects and patients with various pathologies. Three datasets (ADNI, MRBrainS, NAMIC) are publicly available, consisting of 44 healthy volunteers and 10 patients with schizophrenia. Other three in-house datasets, comprising 87 subjects in total, consisted of patients with mild to severe traumatic brain injury, brain tumors, and various movement disorders. A combination of T1-w, T2-w were used to skull-strip these datasets. We show significant improvement in stripping over the competing methods on both healthy and pathological brains. We also show that our multi-contrast framework is robust and maintains accurate performance across different types of acquisitions and scanners, even when using normal brains as atlases to strip pathological brains, demonstrating that our algorithm is applicable even when reference segmentations of pathological brains are not available to be used as atlases.
•A novel multi-contrast patch-based MR brain skullstripping algorithm is proposed.•It is validated on 6 datasets, including subjects with traumatic brain injuries and tumors.•It outperforms 4 state-of-the art methods, both on normal and pathological brains.
To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) ...diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.
Patients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days, and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury.
At enrollment, patients with TBI had increased serum NfL compared to controls (
0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls (
0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.
Serum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI.
This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.
To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.
Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor ...progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks.
Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days.
We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.
Neurofibromatosis type 2 Asthagiri, Ashok R, Dr; Parry, Dilys M, PhD; Butman, John A, MD ...
The Lancet,
06/2009, Letnik:
373, Številka:
9679
Journal Article
Recenzirano
Odprti dostop
Summary Neurofibromatosis type 2 is an autosomal-dominant multiple neoplasia syndrome that results from mutations in the NF2 tumour suppressor gene located on chromosome 22q. It has a frequency of ...one in 25 000 livebirths and nearly 100% penetrance by 60 years of age. Half of patients inherit a germline mutation from an affected parent and the remainder acquire a de novo mutation for neurofibromatosis type 2. Patients develop nervous system tumours (schwannomas, meningiomas, ependymomas, astrocytomas, and neurofibromas), peripheral neuropathy, ophthalmological lesions (cataracts, epiretinal membranes, and retinal hamartomas), and cutaneous lesions (skin tumours). Optimum treatment is multidisciplinary because of the complexities associated with management of the multiple, progressive, and protean lesions associated with the disorder. We review the molecular pathogenesis, genetics, clinical findings, and management strategies for neurofibromatosis type 2.
Purpose
As deep neural networks achieve more success in the wide field of computer vision, greater emphasis is being placed on the generalizations of these models for production deployment. With ...sufficiently large training datasets, models can typically avoid overfitting their data; however, for medical imaging it is often difficult to obtain enough data from a single site. Sharing data between institutions is also frequently nonviable or prohibited due to security measures and research compliance constraints, enforced to guard protected health information (PHI) and patient anonymity.
Methods
In this paper, we implement cyclic weight transfer with independent datasets from multiple geographically disparate sites without compromising PHI. We compare results between single‐site learning (SSL) and multisite learning (MSL) models on testing data drawn from each of the training sites as well as two other institutions.
Results
The MSL model attains an average dice similarity coefficient (DSC) of 0.690 on the holdout institution datasets with a volume correlation of 0.914, respectively corresponding to a 7% and 5% statistically significant improvement over the average of both SSL models, which attained an average DSC of 0.646 and average correlation of 0.871.
Conclusions
We show that a neural network can be efficiently trained on data from two physically remote sites without consolidating patient data to a single location. The resulting network improves model generalization and achieves higher average DSCs on external datasets than neural networks trained on data from a single source.
Summary Background Although the use of magnetic resonance imaging (MRI) for the diagnosis of acute stroke is increasing, this method has not proved more effective than computed tomography (CT) in the ...emergency setting. We aimed to prospectively compare CT and MRI for emergency diagnosis of acute stroke. Methods We did a single-centre, prospective, blind comparison of non-contrast CT and MRI (with diffusion-weighted and susceptibility weighted images) in a consecutive series of patients referred for emergency assessment of suspected acute stroke. Scans were independently interpreted by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. Results 356 patients, 217 of whom had a final clinical diagnosis of acute stroke, were assessed. MRI detected acute stroke (ischaemic or haemorrhagic), acute ischaemic stroke, and chronic haemorrhage more frequently than did CT (p<0·0001, for all comparisons). MRI was similar to CT for the detection of acute intracranial haemorrhage. MRI detected acute ischaemic stroke in 164 of 356 patients (46%; 95% CI 41–51%), compared with CT in 35 of 356 patients (10%; 7–14%). In the subset of patients scanned within 3 h of symptom onset, MRI detected acute ischaemic stroke in 41 of 90 patients (46%; 35–56%); CT in 6 of 90 (7%; 3–14%). Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78–88%) and CT of 26% (56 of 217; 20–32%) for the diagnosis of any acute stroke. Interpretation MRI is better than CT for detection of acute ischaemia, and can detect acute and chronic haemorrhage; therefore it should be the preferred test for accurate diagnosis of patients with suspected acute stroke. Because our patient sample encompassed the range of disease that is likely to be encountered in emergency cases of suspected stroke, our results are directly applicable to clinical practice.
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