The WHO classification since 2016 confirms the importance of integrating molecular diagnosis for prognosis and treatment decisions of adult-type diffuse gliomas. This motivates the development of ...non-invasive diagnostic methods, in particular MRI, to predict molecular subtypes of gliomas before surgery. At present, this development has been focused on deep-learning (DL)-based predictive models, mainly with conventional MRI (cMRI), despite recent studies suggesting multi-shell diffusion MRI (dMRI) offers complementary information to cMRI for molecular subtyping. The aim of this work is to evaluate the potential benefit of combining cMRI and multi-shell dMRI in DL-based models. A model implemented with deep residual neural networks was chosen as an illustrative example. Using a dataset of 146 patients with gliomas (from grade 2 to 4), the model was trained and evaluated, with nested cross-validation, on pre-operative cMRI, multi-shell dMRI, and a combination of the two for the following classification tasks: (i) IDH-mutation; (ii) 1p/19q-codeletion; and (iii) three molecular subtypes according to WHO 2021. The results from a subset of 100 patients with lower grades gliomas (2 and 3 according to WHO 2016) demonstrated that combining cMRI and multi-shell dMRI enabled the best performance in predicting IDH mutation and 1p/19q codeletion, achieving an accuracy of 75 ± 9% in predicting the IDH-mutation status, higher than using cMRI and multi-shell dMRI separately (both 70 ± 7%). Similar findings were observed for predicting the 1p/19q-codeletion status, with the accuracy from combining cMRI and multi-shell dMRI (72 ± 4%) higher than from each modality used alone (cMRI: 65 ± 6%; multi-shell dMRI: 66 ± 9%). These findings remain when we considered all 146 patients for predicting the IDH status (combined: 81 ± 5% accuracy; cMRI: 74 ± 5%; multi-shell dMRI: 73 ± 6%) and for the diagnosis of the three molecular subtypes according to WHO 2021 (combined: 60 ± 5%; cMRI: 57 ± 8%; multi-shell dMRI: 56 ± 7%). Together, these findings suggest that combining cMRI and multi-shell dMRI can offer higher accuracy than using each modality alone for predicting the IDH and 1p/19q status and in diagnosing the three molecular subtypes with DL-based models.
A recent collection of
Lepiota spiculata
from the Dominican Republic is presented here. Macro- and micromorphological features of
L. spiculata
are described in detail, and its evolutionary ...(phylogenetic) position within
Lepiota
sect.
Ovisporae
, in the subincarnata/brunneoincarnata clade, is assessed on the basis of a combined nrLSU + nrITS +
rpb2
+
tef1
analysis. Additionally, high levels of deadly amatoxins were detected and quantified in
L. spiculata
for the first time by HPLC analysis; in particular, α-amanitin was found at concentrations up to approximately 4 mg/g dry weight, which render
L. spiculata
a potentially lethal mushroom, if ingested.
Recessive mutations in GJA12/GJC2, the gene that encodes the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), an early onset dysmyelinating disorder of the CNS, ...characterized by nystagmus, psychomotor delay, progressive spasticity and cerebellar signs. Here we describe three patients from one family with a novel recessively inherited mutation, 99C>G (predicted to cause an Ile>Met amino acid substitution; I33M) that causes a milder phenotype. All three had a late-onset, slowly progressive, complicated spastic paraplegia, with normal or near-normal psychomotor development, preserved walking capability through adulthood, and no nystagmus. MRI and MR spectroscopy imaging were consistent with a hypomyelinating leukoencephalopathy. The mutant protein forms gap junction plaques at cell borders similar to wild-type (WT) Cx47 in transfected cells, but fails to form functional homotypic channels in scrape-loading and dual whole-cell patch clamp assays. I33M forms overlapping gap junction plaques and functional channels with Cx43, however, I33M/Cx43 channels open only when a large voltage difference is applied to paired cells. These channels probably do not function under physiological conditions, suggesting that Cx47/Cx43 channels between astrocytes and oligodendrocytes are disrupted, similar to the loss-of-function endoplasmic reticulum-retained Cx47 mutants that cause PMLD. Thus, GJA12/GJC2 mutations can result in a milder phenotype than previously appreciated, but whether I33M retains a function of Cx47 not directly related to forming functional gap junction channels is not known.
Purpose
Functional MRI is not routinely used for neurosurgical planning despite potential important advantages, due to difficulty of determining quality. We introduce a novel method for objective ...evaluation of fMRI scan quality, based on activation maps. A template matching analysis (TMA) is presented and tested on data from two clinical fMRI protocols, performed by healthy controls in seven clinical centers. Preliminary clinical utility is tested with data from low-grade glioma patients.
Methods
Data were collected from 42 healthy subjects from seven centers, with standardized finger tapping (FT) and verb generation (VG) tasks. Copies of these “typical” data were deliberately analyzed incorrectly to assess feasibility of identifying them as “atypical.” Analyses of the VG task administered to 32 tumor patients assessed sensitivity of the TMA method to anatomical abnormalities.
Results
TMA identified all atypical activity maps for both tasks, at the cost of incorrectly classifying 3.6 (VG)–6.5% (FT) of typical maps as atypical. For patients, the average TMA was significantly higher than atypical healthy scans, despite localized anatomical abnormalities caused by a tumor.
Conclusion
This study supports feasibility of TMA for objective identification of atypical activation patterns for motor and verb generation fMRI protocols. TMA can facilitate the use and evaluation of clinical fMRI in hospital settings that have limited access to fMRI experts. In a clinical setting, this method could be applied to automatically flag fMRI scans showing atypical activation patterns for further investigation to determine whether atypicality is caused by poor scan data quality or abnormal functional topography.
Functional magnetic resonance (fMR) imaging and diffusion MR tractography have emerged as valuable tools in the evaluation of verbal language in brain tumor patients, and have changed the way ...neurosurgeons look at patients with a mass in the dominant hemisphere. The techniques have obtained recognition as valuable presurgical clinical tools in the determination of hemispheric dominance and in the selection of candidates who may benefit from awake craniotomy. In the near future fMRI and diffusion MR Tractography may contribute to elucidate mechanisms of brain plasticity and may provide predictors of favorable postoperative clinical outcome. The functional anatomy of the language network and the role of fMR imaging and diffusion MR tractography in the evaluation of patients with a brain tumor are the focus of this article.
Glioblastoma extensively infiltrates the brain; despite surgery and aggressive therapies, the prognosis is poor. A multidisciplinary approach combining mathematical, clinical and radiological data ...has the potential to foster our understanding of glioblastoma evolution in every single patient, with the aim of tailoring therapeutic weapons. In particular, the ultimate goal of biomathematics for cancer is the identification of the most suitable theoretical models and simulation tools, both to describe the biological complexity of carcinogenesis and to predict tumor evolution. In this report, we describe the results of a critical review about different mathematical models in neuro-oncology with their clinical implications. A comprehensive literature search and review for English-language articles concerning mathematical modelling in glioblastoma has been conducted. The review explored the different proposed models, classifying them and indicating the significative advances of each one. Furthermore, we present a specific case of a glioblastoma patient in which our recently proposed innovative mechanical model has been applied. The results of the mathematical models have the potential to provide a relevant benefit for clinicians and, more importantly, they might drive progress towards improving tumor control and patient's prognosis. Further prospective comparative trials, however, are still necessary to prove the impact of mathematical neuro-oncology in clinical practice.
Two new species of
Lepiota
(
L. squamulodiffracta
and
L. sosuensis
) and a new record (
L. subgranulosa
) are described based on collections made in the Dominican Republic. The phylogenetic position ...of the species based on nrITS data is analyzed and discussed.
L. squamulodiffracta
belongs in section
Lepiota
, and it is characterized by the velar patches on pileus split up into numerous minute squamules, striate-sulcate pileus up to the center, and penguin-shaped spores.
L. sosuensis
has overall white basidiocarps, dextrinoid and metachromatic spores, trichodermial pileus covering, and rare clamp-connections.
L. subgranulosa
stands out morphologically by the spurred spores with one or several protuberances that give the spores an irregular outline.
Abstract Brown–Vialetto–van Laere (BVVL) and Fazio–Londe (FL) are rare and clinically overlapping motor neurons syndromes. Recently BVVL has been associated with mutations in C20orf54/hRFT2 and ...defective riboflavin transport. We compared clinical and laboratory features of 6 patients (age range 11–17 years), with features of BVVL and FL overlap syndromes. Patients were assessed as following: blood levels of riboflavin and redox status, electrophysiological, neuroradiological and pulmonary studies, ALS functional rating scale and molecular genetic analysis. Two patients manifested deafness at ages of 3 and 10 years, and developed later subacute progressive ponto-bulbar palsy. A third patient markedly improved after intravenous immunoglobulins (IVIG), but then relapsed remaining unresponsive to treatment; he was not deaf although had abnormal auditory evoked responses (BAERs). The remaining 3 patients had no deafness, although likewise manifested subacute progressive ponto-bulbar palsy. We found hRFT2 mutations in 3/6 patients manifesting deafness or abnormal BAERs. No patient had reduced riboflavin blood levels. However, on riboflavin supplementation (10 mg/kg/day) the most severely affected BVVL patient stopped progression of symptoms following 8 months of treatment. BVVL and FL are severe progressive diseases with overlapping symptoms although only hRFT2 mutated patients manifest deafness. Riboflavin supplementation seems to stabilize and improve progression of the disease.
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