Imaging-Based 3-Dimensional Printing for Improved Maxillofacial Presurgical Planning: A Single Center Case Series.

PURPOSE: 3-D printing is an increasingly widespread technology that allows physical models to be constructed based on cross-sectional medical imaging data. We sought to develop a pipeline for production of 3-dimensional (3-D) models for presurgical planning and assess the value of these models for surgeons and patients. METHODS: In this institutional review board-approved, single-center case series, participating surgeons identified cases for 3-D model printing, and after obtaining patient consent, a 3-D model was produced for each of the 7 participating patients based on preoperative cross-sectional imaging. Each model was given to the surgeon to use during the surgical consent discussion and preoperative planning. Patients and surgeons completed questionnaires evaluating the quality and usefulness of the models. RESULTS: The 3-D models improved surgeon confidence in their operative approach, influencing the choice of operative approach in the majority of cases. Patients and surgeons reported that the model improved patient comprehension of the surgery during the consent discussion, including risks and benefits of the surgery. Model production time was as little as 4 days, and the average per-model cost was $350. CONCLUSIONS: 3-D printed models are useful presurgical tools from both surgeon and patient perspectives. Development of local hospital-based 3-D printing capabilities enables model production with rapid turnaround and modest cost, representing a value-added service for radiologists to offer their surgical colleagues.

Development and Evaluation of a Competency-Based Anatomy Rotation for Diagnostic Radiology Residents During Internship Year: A Canadian Experience.

RATIONALE AND AIM: As medical schools reduce the hours of anatomy teaching, residents in anatomy-intensive residency programs like radiology must independently acquire the anatomy knowledge needed to achieve competency. The purpose of this study was to develop and evaluate a 4-week competency-based self-directed anatomy rotation for junior residents. METHODS: Seven post-graduate year 1 (PGY-1) radiology residents completed a 4-week rotation of radiologic anatomy. The objectives were developed from standards, senior residents, and expert opinion, and the competency-based curriculum included self-directed modules. Pre-course and post-course tests were administered and test scores were compared using an unpaired t test. In addition, PGY-1 residents completed a course evaluation and survey regarding their anatomy knowledge and anatomy exposure prior to completing the course. RESULTS: Out of the 25 points available, the average pre-test score was 10.79 ± 2.78 (range 8-16.5), and the average post-test score was 21.64 ± 2.23 (range 18.5-25). This difference was statistically significant (P < .0001). The PGY-1 residents reported receiving < 10% of dedicated radiologic anatomy teaching prior to residency and felt unprepared for the anatomy required in residency. Overall, residents felt more confident in looking at images after completing the self-directed radiologic anatomy course. CONCLUSION: This study demonstrates the feasibility of creating a self-directed course for radiology residents that significant improves their anatomy knowledge. Given the trend in medical undergraduate education away from dedicated anatomy teaching, residency programs should consider addressing anatomy education more formally for junior residents to ensure that trainees receive the foundational knowledge required for residency.

Canadian Association of Radiologists White Paper on Artificial Intelligence in Radiology.

Artificial intelligence (AI) is rapidly moving from an experimental phase to an implementation phase in many fields, including medicine. The combination of improved availability of large datasets, increasing computing power, and advances in learning algorithms has created major performance breakthroughs in the development of AI applications. In the last 5 years, AI techniques known as deep learning have delivered rapidly improving performance in image recognition, caption generation, and speech recognition. Radiology, in particular, is a prime candidate for early adoption of these techniques. It is anticipated that the implementation of AI in radiology over the next decade will significantly improve the quality, value, and depth of radiology's contribution to patient care and population health, and will revolutionize radiologists' workflows. The Canadian Association of Radiologists (CAR) is the national voice of radiology committed to promoting the highest standards in patient-centered imaging, lifelong learning, and research. The CAR has created an AI working group with the mandate to discuss and deliberate on practice, policy, and patient care issues related to the introduction and implementation of AI in imaging. This white paper provides recommendations for the CAR derived from deliberations between members of the AI working group. This white paper on AI in radiology will inform CAR members and policymakers on key terminology, educational needs of members, research and development, partnerships, potential clinical applications, implementation, structure and governance, role of radiologists, and potential impact of AI on radiology in Canada.

Intermolecular transmission of superoxide dismutase 1 misfolding in living cells.

Human wild-type superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), in double transgenic models of FALS, and in cell culture systems, but the structural determinants of this process are unclear. Here we molecularly dissect the effects of intracellular and cell-free obligately misfolded SOD1 mutant proteins on natively structured wild-type SOD1. Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Expression of G127X and G85R in mouse cell lines did not induce misfolding of murine wtSOD1, and a species restriction element for human wtSOD1 conversion was mapped to a region of sequence divergence in loop II and ß-strand 3 of the SOD1 ß-barrel (residues 24-36), then further refined surprisingly to a single tryptophan residue at codon 32 (W32) in human SOD1. Time course experiments enabled by W32 restriction revealed that G127X and misfolded wtSOD1 can induce misfolding of cell-endogenous wtSOD1. Finally, aggregated recombinant G127X is capable of inducing misfolding and protease sensitivity of recombinant human wtSOD1 in a cell-free system containing reducing and chelating agents; cell-free wtSOD1 conversion was also restricted by W32. These observations demonstrate that misfolded SOD1 can induce misfolding of natively structured wtSOD1 in a physiological intracellular milieu, consistent with a direct protein-protein interaction.

Using immersive technology and architectural design to assist head and neck cancer patients' recovery from treatment: A focus group and technology acceptance study.

PURPOSE: Head and neck cancer patients can face debilitating treatment related side-effects, resulting in requirement for support and negatively impacting on care outcomes. This study aimed to develop a digital recovery support package and assess its acceptability with head and neck cancer patients to support their information needs and assist with their self-management. It provided additional support through development of a WebXR platform 'recovery' package, which allowed patients to live a 'virtual reality' experience, entering and moving inside a 'virtual room', accessing targeted resources and specific learning materials related to their cancer. METHOD: A qualitative intervention development study consisting of three phases. This study followed the COREQ checklist for qualitative research. Phase 1- Focus groups with seven head and neck cancer patients and six healthcare professionals. Phase 2- Development of 'recovery' package based on the focus group data which informed the content and design of the WebXR recovery platform. Phase 3- Technology acceptance study. Once developed, the platform's acceptability of the experience lived inside the virtual room was assessed via qualitative interviews with six different patient participants. RESULTS: Most participants felt comfortable using the virtual reality platform, finding it a realistic and useful support for identifying resources and signposting to relevant materials. Participants agreed the WebXR platform was a feasible tool for the head and neck cancer setting and helped reduce anxiety. CONCLUSIONS: Head and neck cancer patients welcome specific targeted, information and advice to support their ability to self-manage their rehabilitation and thus focus their nursing care. The platform was implemented during the Covid-19 pandemic, demonstrating its versatility and accessibility in providing complementary support to head and neck cancer patients, to empower them to adjust to their 'new' normal as part of their ongoing cancer journeys.

Transvenous Approaches to Embolization of Dural Arteriovenous Fistulae of the Cavernous Sinus.

Dural arteriovenous fistulae of the cavernous sinus (CS) (previously often referred to indirect carotid cavernous fistulas) are rare vascular shunts involving meningeal branches and osseous branches of the external or internal carotid arteries and the CS. They typically present with ocular symptoms including pain, conjunctival injection, and proptosis. Left untreated there may be a risk of vision loss, and fistulas with cortical venous reflux through either the deep or superficial venous system may cause intracranial venous congestion or hemorrhage. Endovascular embolization is the standard treatment, and while transarterial routes may appear possible, transarterial embolization has considerable risks of ischemic complications. Conversely, transvenous routes achieve a high rate of fistula occlusion with a low risk of peri-procedural morbidity. Procedural success depends on identification of the venous outflows from the fistula and localization of the fistulous point, to select the best route of access to the CS, including the inferior petrosal sinus (IPS), intercavernous sinus, or superior ophthalmic vein, among others. Even if the IPS is not visualized, it may be possible to recanalize it to gain access to the CS. Embolization can be performed with a combination of coils, fibered coils, and liquid embolic agents, focusing on occlusion of the fistulous point or blocking high-risk venous outflow pathways. In this review we will highlight procedural pearls and potential pitfalls and our typical approach to these lesions based on illustrative examples.

A theory for the anisotropic and inhomogeneous dielectric properties of proteins.

Using results from the dielectric theory of polar solids and liquids, we calculate the mesoscopic, spatially-varying dielectric constant at points in and around a protein by combining a generalization Kirkwood-Fröhlich theory along with short all-atom molecular dynamics simulations of equilibrium protein fluctuations. The resulting dielectric permittivity tensor is found to exhibit significant heterogeneity and anisotropy in the protein interior. Around the surface of the protein it may exceed the dielectric constant of bulk water, especially near the mobile side chains of polar residues, such as K, N, Q, and E. The anisotropic character of the protein dielectric selectively modulates the attractions and repulsions between charged groups in close proximity.

Toward a mechanism of prion misfolding and structural models of PrP(Sc): current knowledge and future directions.

Despite extensive investigation, many features of prion protein misfolding remain enigmatic. Physicochemical variables known to influence misfolding are reviewed to help elucidate the mechanism of prionogenesis and identify salient features of PrP(Sc), the misfolded conformer of the prion protein. Prospective work on refinement of candidate PrP(Sc) models based on thermodynamic considerations will help to complete atomic-scale structural details missing from experimental studies and may explain the basis for the templating activity of PrP(Sc) in disease.

Generalization of the prion hypothesis to other neurodegenerative diseases: an imperfect fit.

Protein misfolding diseases have been classically understood as diffuse errors in protein folding, with misfolded protein arising autonomously throughout a tissue due to a pathologic stressor. The field of prion science has provided an alternative mechanism whereby a seed of pathologically misfolded protein, arising exogenously or through a rare endogenous structural fluctuation, yields a template to catalyze misfolding of the native protein. The misfolded protein may then spread intercellularly to communicate the misfold to adjacent areas and ultimately infect a whole tissue. Mounting evidence implicates a prion-like process in the propagation of several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and the tauopathies. However, the parallels between the events observed in these conditions and those in prion disease are often incomplete. The aim of this review was to examine the current state of knowledge concerning the mechanisms of protein misfolding and aggregation for neurodegeneration-associated proteins. In addition, possible methods of intercellular spread are described that focus on the hypothesis that released microvesicles function as misfolded protein delivery vehicles, and the therapeutic options enabled by viewing these diseases from the prion perspective.

Brain Arteriovenous Malformations: The Role of Imaging in Treatment Planning and Monitoring Response.

Brain arteriovenous malformations (AVMs) are characterized by shunting between pial arteries and cortical or deep veins, with the presence of an intervening nidus of tortuous blood vessels. These lesions present a therapeutic challenge, because their natural history entails a risk of intracranial hemorrhage, but treatment may cause significant morbidity. In this article, imaging features of AVMs on MR imaging and catheter angiography are reviewed to stratify the risk of hemorrhage and guide appropriate management. The angioarchitecture of AVMs may evolve over time, spontaneously or in response to treatment, necessitating ongoing imaging surveillance.

Electrostatics in the stability and misfolding of the prion protein: salt bridges, self energy, and solvation.

Using a recently developed mesoscopic theory of protein dielectrics, we have calculated the salt bridge energies, total residue electrostatic potential energies, and transfer energies into a low dielectric amyloid-like phase for 12 species and mutants of the prion protein. Salt bridges and self energies play key roles in stabilizing secondary and tertiary structural elements of the prion protein. The total electrostatic potential energy of each residue was found to be invariably stabilizing. Residues frequently found to be mutated in familial prion disease were among those with the largest electrostatic energies. The large barrier to charged group desolvation imposes regional constraints on involvement of the prion protein in an amyloid aggregate, resulting in an electrostatic amyloid recruitment profile that favours regions of sequence between alpha helix 1 and beta strand 2, the middles of helices 2 and 3, and the region N-terminal to alpha helix 1. We found that the stabilization due to salt bridges is minimal among the proteins studied for disease-susceptible human mutants of prion protein.

Partial thrombosis of an anterior communicating artery aneurysm prior to endovascular coiling, with intra-procedural distal thrombus embolization.

Thromboembolic stroke from migration of thrombus formed in non-giant intracranial aneurysms is a recognized but rare event. We describe a case of partial thrombosis of a 7 mm anterior communicating artery aneurysm, which embolized to the right callosomarginal artery in the brief time interval between two sequential diagnostic angiograms performed as part of elective endovascular coiling, and before any instrumentation had been advanced into the intracranial circulation. To our knowledge, this is the first reported case of aneurysmal thrombus embolization observed angiographically in near real time.

Immunological mimicry of PrPC-PrPSc interactions: antibody-induced PrP misfolding.

Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to an abnormal protease-resistant conformational isoform (PrP(Sc)) by template-directed conversion. The interaction between PrP(C) and PrP(Sc) is mediated by specific sites which have been mapped to six putative 'binding and conversion domains' (PrP-BCD) through peptide and antibody competition studies. Monoclonal antibodies (mAbs) directed against the bityrosine motif Tyr-Tyr-Arg (YYR) specifically recognize PrP(Sc) and other misfolded PrP species. Here, we report that select bead-bound PrP-BCD mAbs induce exposure of bityrosine epitopes on mouse brain PrP. By competition immunoprecipitation, we show that PrP-BCD mAb-induced bityrosine exposure occurs at alpha-helices 1 and 3. However, PrP-BCD mAb-induced PrP(C) misfolding is not accompanied by beta-sheet dissociation, a key event in PrP(C) conversion to PrP(Sc), and is not associated with acquisition of protease resistance, or the capacity to recruit additional molecules of PrP. Our data suggest that mAb mimics of the physical interaction of PrP(C) with PrP(Sc) can induce unfolding of specific PrP domains, but that subsequent processes (including the energetically unfavorable beta-sheet dissociation) effect isoform conversion in prion disease.