Vertebrae segmentation in reduced radiation CT imaging for augmented reality applications.
International journal of computer assisted radiology and surgery
PURPOSE: There is growing evidence for the use of augmented reality (AR) navigation in spinal surgery to increase surgical accuracy and improve clinical outcomes. Recent research has employed AR techniques to create accurate auto-segmentations, the basis of patient registration, using reduced radiation dose intraoperative computed tomography images. In this study, we aimed to determine if spinal surgery AR applications can employ reduced radiation dose preoperative computed tomography (pCT) images.METHODS: We methodically decreased the imaging dose, with the addition of Gaussian noise, that was introduced into pCT images to determine the image quality threshold that was required for auto-segmentation. The Gaussian distribution's standard deviation determined noise level, such that a scalar multiplier (L: [0.00, 0.45], with steps of 0.03) simulated lower doses as L increased. We then enhanced the images with denoising algorithms to evaluate the effect on the segmentation.RESULTS: The pCT radiation dose was decreased to below the current lowest clinical threshold and the resulting images produced segmentations that were appropriate for input into AR applications. This held true at simulated dose L=0.06 (estimated 144 mAs) but not at L=0.09 (estimated 136 mAs). The application of denoising algorithms to the images resulted in increased artifacts and decreased bone density.CONCLUSIONS: The pCT image quality that is required for AR auto-segmentation is lower than that which is currently employed in spinal surgery. We recommend a reduced radiation dose protocol of approximately 140 mAs. This has the potential to reduce the radiation experienced by patients in comparison to procedures without AR support. Future research is required to identify the specific, clinically relevant radiation dose thresholds required for surgical navigation.
View details for DOI 10.1007/s11548-022-02561-y
View details for PubMedID 35025073
Autocatalytic-protection for an unknown locus CRISPR-Cas countermeasure for undesired mutagenic chain reactions.
Journal of theoretical biology
2021; 528: 110831
The mutagenic chain reaction (MCR) is a genetic tool to use a CRISPR-Cas construct to introduce a homing endonuclease, allowing gene drive to influence whole populations in a minimal number of generations (Esvelt et al., 2014; Gantz and Bier, 2015; Gantz and Bier, 2016). The question arises: if an active genetic terror event is released into a population, could we prevent the total spread of the undesired allele (Gantz, et al., 2015; Webber et al., 2015)? Thus far, effective protection methods require knowledge of the terror locus (Grunwald et al., 2019). Here we introduce a novel approach, an autocatalytic-Protection for an Unknown Locus (a-PUL), whose aim is to spread through a population and arrest and decrease an active terror event's spread without any prior knowledge of the terror-modified locus, thus allowing later natural selection and ERACR drives to restore the normal locus (Hammond et al., 2017). a-PUL, using a mutagenic chain reaction, includes (i) a segment encoding a non-Cas9 endonuclease capable of homology-directed repair suggested as Type II endonuclease Cpf1 (Cas12a), (ii) a ubiquitously-expressed gene encoding a gRNA (gRNA1) with a U4AU4 3'-overhang specific to Cpf1 and with crRNA specific to some desired genomic sequence of non-coding DNA, (iii) a ubiquitously-expressed gene encoding two gRNAs (gRNA2/gRNA3) both with tracrRNA specific to Cas9 and crRNA specific to two distinct sites of the Cas9 locus, and (iv) homology arms flanking the Cpf1/gRNA1/gRNA2/gRNA3 cassette that are identical to the region surrounding the target cut directed by gRNA1 (Khan, 2016; Zetsche et al., 2015). We demonstrate the proof-of-concept and efficacy of our protection construct through a Graphical Markov model and computer simulation.
View details for DOI 10.1016/j.jtbi.2021.110831
View details for PubMedID 34274311
On the relation of gene essentiality to intron structure: a computational and deep learning approach
LIFE SCIENCE ALLIANCE
2021; 4 (6)
Essential genes have been studied by copy number variants and deletions, both associated with introns. The premise of our work is that introns of essential genes have distinct characteristic properties. We provide support for this by training a deep learning model and demonstrating that introns alone can be used to classify essentiality. The model, limited to first introns, performs at an increased level, implicating first introns in essentiality. We identify unique properties of introns of essential genes, finding that their structure protects against deletion and intron-loss events, especially centered on the first intron. We show that GC density is increased in the first introns of essential genes, allowing for increased enhancer activity, protection against deletions, and improved splice site recognition. We find that first introns of essential genes are of remarkably smaller size than their nonessential counterparts, and to protect against common 3' end deletion events, essential genes carry an increased number of (smaller) introns. To demonstrate the importance of the seven features we identified, we train a feature-based model using only these features and achieve high performance.
View details for DOI 10.26508/lsa.202000951
View details for Web of Science ID 000654748200008
View details for PubMedID 33906938
View details for PubMedCentralID PMC8127325
Lateralized Deficits in Motor, Sensory, and Olfactory Domains in Dementia
JOURNAL OF ALZHEIMERS DISEASE
2021; 79 (3): 1033-1040
There exist functional deficits in motor, sensory, and olfactory abilities in dementias. Measures of these deficits have been discussed as potential clinical markers.We measured the deficit of motor, sensory, and olfactory functions on both the left and right body side, to study potential body lateralizations.This IRB-approved study (N = 84) performed left/right clinical tests of gross motor (dynamometer test), sensory (Von Frey test), and olfactory (peppermint oil test) ability. The Mini-Mental Status Exam was administered to determine level of dementia; medical and laboratory data were collected.Sensory and olfactory deficits lateralized to the left side of the body, while motor deficits lateralized to the right side. We found clinical correlates of motor lateralization: female, depression, MMSE <15, and diabetes. While clinical correlates of sensory lateralization: use of psychotherapeutic agent, age ≥85, MMSE <15, and male. Lastly, clinical correlates of olfactory lateralization: age <85, number of medications >10, and male.These lateralized deficits in body function can act as early clinical markers for improved diagnosis and treatment. Future research should identify correlates and corresponding therapies to strengthen at-risk areas.
View details for DOI 10.3233/JAD-201216
View details for Web of Science ID 000618072600010
View details for PubMedID 33459707
OnabotulinumtoxinA injections: treatment of reversible cerebral vasoconstriction syndrome chronic daily headaches
BMJ CASE REPORTS
2019; 12 (5)
Reversible cerebral vasoconstriction syndrome (RCVS) is a rare condition characterised by repetitive, multifocal, vasofluctuations of cerebral arteries. A key symptom is chronic, disabling 'thunderclap' headaches, which are extremely difficult to treat as established medications may exacerbate the pathophysiology of RCVS. OnabotulinumtoxinA (OBT-A) injections are used for the prophylaxis of chronic daily headaches (CDH). The mechanism of action of OBT-A significantly differs from oral headache treatments. Thus, OBT-A may be an effective, safe treatment of RCVS-CDH. A 51-year-old woman with RCVS-CDH presented to outpatient clinic. This case report describes the first, believed, documented treatment of RCVS-CDH by OBT-A injections. In 2018, the consented patient received a total of 200 units of OBT-A, 155 units to the 31 approved U.S. Food and Drug Administration (FDA) sites and 45 units injected into the bilateral occipital belly of occipitofrontalis muscles. The patient reported 3 months of excellent pain relief (60% reduction). Three rounds of OBT-A injection, each 3 months apart, resulted in 80% reduction. OBT-A injections may prove a successful, novel treatment for RCVS-CDH.
View details for DOI 10.1136/bcr-2018-228562
View details for Web of Science ID 000661395200086
View details for PubMedID 31151973
View details for PubMedCentralID PMC6557340