In image-guided neurosurgery, a registration between the patient and their pre-operative images and the tracking of surgical tools enables GPS-like guidance to the surgeon. However, factors such as ...brainshift, image distortion, and registration error cause the patient-to-image alignment accuracy to degrade throughout the surgical procedure no longer providing accurate guidance. The authors present a gesture-based method for manual registration correction to extend the usage of augmented reality (AR) neuronavigation systems. The authors’ method, which makes use of the touchscreen capabilities of a tablet on which the AR navigation view is presented, enables surgeons to compensate for the effects of brainshift, misregistration, or tracking errors. They tested their system in a laboratory user study with ten subjects and found that they were able to achieve a median registration RMS error of 3.51 mm on landmarks around the craniotomy of interest. This is comparable to the level of accuracy attainable with previously proposed methods and currently available commercial systems while being simpler and quicker to use. The method could enable surgeons to quickly and easily compensate for most of the observed shift. Further advantages of their method include its ease of use, its small impact on the surgical workflow and its small-time requirement.
Bardet-Biedl syndrome (BBS), an emblematic disease in the rapidly evolving field of ciliopathies, is characterized by pleiotropic clinical features and extensive genetic heterogeneity. To date, 14 ...BBS genes have been identified, 3 of which have been found mutated only in a single BBS family each (BBS11/TRIM32, BBS13/MKS1 and BBS14/MKS4/NPHP6). Previous reports of systematic mutation detection in large cohorts of BBS families (n > 90) have dealt only with a single gene, or at most small subsets of the known BBS genes. Here we report extensive analysis of a cohort of 174 BBS families for 12/14 genes, leading to the identification of 28 novel mutations. Two pathogenic mutations in a single gene have been found in 117 families, and a single heterozygous mutation in 17 families (of which 8 involve the BBS1 recurrent mutation, M390R). We confirm that BBS1 and BBS10 are the most frequently mutated genes, followed by BBS12. No mutations have been found in BBS11/TRIM32, the identification of which as a BBS gene only relies on a single missense mutation in a single consanguineous family. While a third variant allele has been observed in a few families, they are in most cases missenses of uncertain pathogenicity, contrasting with the type of mutations observed as two alleles in a single gene. We discuss the various strategies for diagnostic mutation detection, including homozygosity mapping and targeted arrays for the detection of previously reported mutations.
Careful trajectory planning on preoperative vascular imaging is an essential step in deep brain stimulation (DBS) to minimize risks of hemorrhagic complications and postoperative neurological ...deficits. This paper compares 2 MRI methods for visualizing cerebral vasculature and planning DBS probe trajectories: a single data set T1-weighted scan with double-dose gadolinium contrast (T1w-Gd) and a multi–data set protocol consisting of a T1-weighted structural, susceptibility-weighted venography, and time-of-flight angiography (T1w-SWI-TOF). Two neurosurgeons who specialize in neuromodulation surgery planned bilateral STN DBS in 18 patients with Parkinson's disease (36 hemispheres) using each protocol separately. Planned trajectories were then evaluated across all vascular data sets (T1w-Gd, SWI, and TOF) to detect possible intersection with blood vessels along the entire path via an objective vesselness measure. The authors' results show that trajectories planned on T1w-SWI-TOF successfully avoided the cerebral vasculature imaged by conventional T1w-Gd and did not suffer from missing vascular information or imprecise data set registration. Furthermore, with appropriate planning and visualization software, trajectory corridors planned on T1w-SWI-TOF intersected significantly less fine vasculature that was not detected on the T1w-Gd (p < 0.01 within 2 mm and p < 0.001 within 4 mm of the track centerline). The proposed T1w-SWI-TOF protocol comes with minimal effects on the imaging and surgical workflow, improves vessel avoidance, and provides a safe cost-effective alternative to injection of gadolinium contrast.
Although 80% of childhood acute lymphoblastic leukemia (ALL) cases are cured with current treatment protocols, exposure to chemotherapeutics or radiation therapy during a vulnerable period of child ...development has been associated with a high frequency of late adverse effects (LAE). Previous observations suggest important skeletal muscle size, density and function deficits in ALL survivors.
Given that only a fraction of all patients will suffer from this particular complication, we investigated whether it could be predicted by genetic markers.
We analysed associations between skeletal muscle force (Fmax) and power (Pmax) and germline genetic variants from 1039 genes derived through whole-exome sequencing. Top-ranking association signals retained after correction for multiple testing were confirmed through genotyping, and further analysed through stratified analyses and multivariate models.
Our results show that skeletal muscle function deficit is associated with two common single nucleotide polymorphisms (SNPs) (rs2001616
=0.0002 (Pmax) and rs41270041
,
=0.02 (Fmax)) and two rare ones located in the
gene
=0.001 (Pmax)). These associations were further modulated by sex, body mass index and risk groups, which reflected glucocorticoid dose and radiation therapy (
≤0.02).
Occurrence of muscle function deficit in childhood ALL is thus strongly modulated by variations in the
and
genes, which could lead to personalized prevention strategies in childhood ALL survivors.
To identify genetic markers associated with late treatment-related skeletal morbidity in survivors of childhood acute lymphoblastic leukemia (ALL).
To this end, we measured the association between ...reduction in bone mineral density or vertebral fractures prevalence and variants from 1039 genes derived through whole exome sequencing in 242 childhood ALL survivors. Top-ranking variants were confirmed through genotyping, and further explored with stratified analyses and multivariable models.
The minor allele of rs1944294 in
gene was associated with bone geometrical parameter, trabecular cross-sectional area (p = 0.001). The association was modulated by radiation therapy (p = 0.001) and post-treatment time (p = 0.0002).
The variant in
gene is a potential novel risk factor of bone morbidity in survivors of childhood ALL.
Careful trajectory planning on preoperative vascular imaging is an essential step in deep brain stimulation (DBS) to minimize risks of hemorrhagic complications and postoperative neurological ...deficits. This paper compares 2 MRI methods for visualizing cerebral vasculature and planning DBS probe trajectories: a single data set T1-weighted scan with double-dose gadolinium contrast (T1w-Gd) and a multi-data set protocol consisting of a T1-weighted structural, susceptibility-weighted venography, and time-of-flight angiography (T1w-SWI-TOF). Two neurosurgeons who specialize in neuromodulation surgery planned bilateral STN DBS in 18 patients with Parkinson's disease (36 hemispheres) using each protocol separately. Planned trajectories were then evaluated across all vascular data sets (T1w-Gd, SWI, and TOF) to detect possible intersection with blood vessels along the entire path via an objective vesselness measure. The authors' results show that trajectories planned on T1w-SWI-TOF successfully avoided the cerebral vasculature imaged by conventional T1w-Gd and did not suffer from missing vascular information or imprecise data set registration. Furthermore, with appropriate planning and visualization software, trajectory corridors planned on T1w-SWI-TOF intersected significantly less fine vasculature that was not detected on the T1w-Gd (p < 0.01 within 2 mm and p < 0.001 within 4 mm of the track centerline). The proposed T1w-SWI-TOF protocol comes with minimal effects on the imaging and surgical workflow, improves vessel avoidance, and provides a safe cost-effective alternative to injection of gadolinium contrast.
Chronic granulomatous disease should be considered in adults of any age in the presence of refractory and/or atypical or fulminant pulmonary infections. This case of new large deletions in NCF1 was ...presented with mulch pneumonitis without a significant history of infections.
Image-guided neurosurgery, or neuronavigation, has been used to visualise the location of a surgical probe by mapping the probe location to pre-operative models of a patient's anatomy. One common ...limitation of this approach is that it requires the surgeon to divert their attention away from the patient and towards the neuronavigation system. In order to improve this type of application, the authors designed a system that sonifies (i.e. provides audible feedback of) distance information between a surgical probe and the location of the anatomy of interest. A user study (n = 15) was completed to determine the utility of sonified distance information within an existing neuronavigation platform (Intraoperative Brain Imaging System (IBIS) Neuronav). The authors’ results were consistent with the idea that combining auditory distance cues with existing visual information from image-guided surgery systems may result in greater accuracy when locating specified points on a pre-operative scan, thereby potentially reducing the extent of the required surgical openings, as well as potentially increasing the precision of individual surgical tasks. Further, the authors’ results were also consistent with the hypothesis that combining auditory and visual information reduces the perceived difficulty in locating a target location within a three-dimensional volume.
Summary
MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was examined for pre‐clinical activity in chronic lymphocytic leukaemia (CLL). A phase II clinical trial was ...performed, starting at a dose of 85 mg/d, three times per week. Dose escalation to 110 mg or the addition of rituximab was permitted in patients without a response after two or more cycles. MGCD0103 demonstrated pre‐clinical activity against CLL cells with a LC50 (concentration lethal to 50%) of 0·23 μmol/l and increased acetylation of the HDAC class I specific target histone H3. Twenty‐one patients received a median of two cycles of MGCD0103 (range, 0–12). All patients had previously received fludarabine, 33% were fludarabine refractory, and 71% had del(11q22·3) or del(17p13·1). No responses according to the National Cancer Institutes 1996 criteria were observed. Three patients received 110 mg and four patients received concomitant rituximab, with no improvement in response. Grade 3–4 toxicity consisted of infections, thrombocytopenia, anaemia, diarrhoea, and fatigue. HDAC inhibition was observed in six out of nine patients on day 8. Limited activity was observed with single agent MGCD0103 in high risk patients with CLL. Future investigations in CLL should focus on broad HDAC inhibition, combination strategies, and approaches to diminish constitutional symptoms associated with this class of drugs.
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