Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol.

BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.

MRI-detected intraosseous bone marrow edema recedes after effective therapy of periodontitis.

OBJECTIVES: T2 STIR MRI sequences can detect preclinical changes associated with periodontal inflammation, i.e. intraosseous edema in the tooth-supporting bone. In this study, we assessed whether MRI can be used for monitoring periodontal disease. MATERIAL AND METHODS: In a prospective cohort study, we examined 35 patients with periodontitis between 10/2018 and 04/2019 by using 3D isotropic T2-weighted short tau inversion recovery (STIR) and Fast Field Echo T1-weighted Black bone sequences. All patients received standardized clinical exams before and three months after non-surgical periodontal therapy. Bone marrow edema extent was quantified in the STIR sequence at 922 sites before and after treatment. Results were compared with standard clinical findings. Non-parametric statistical analysis was performed. RESULTS: Non-surgical periodontal treatment caused significant improvement in mean probing depth (p < 0.001) and frequency of bleeding on probing (p < 0.001). The mean depth of osseous edema per site was reduced from a median [IQR] of 2 [1, 3] mm at baseline to 1 [0, 3] mm, (p < 0.001). Periodontal treatment reduced the frequency of sites with edema from 35 to 24% (p < 0.01). CONCLUSION: The decrease of periodontal bone marrow edema, as observed with T2 STIR MR imaging, is indicative of successful periodontal healing. CLINICAL RELEVANCE STATEMENT: T2 STIR hyperintense bone marrow edema in the periodontal bone decreases after treatment and can therefore be used to evaluate treatment success. Furthermore, MRI reveals new options to depict hidden aspects of periodontitis. KEY POINTS: • T2 STIR hyperintense periodontal intraosseous edema was prospectively investigated in 35 patients with periodontitis before and after treatment and compared to clinical outcomes. • The frequency of affected sites was reduced from 35 to 24% (p < 0.001), and mean edema depth was reduced from a median [IQR] of 2 [1, 3] mm at baseline to 1 [0, 3] mm 3 months after treatment. (p < 0.001). • T2 STIR sequences can be used to monitor the posttreatment course of periodontitis.

Visualization of clinically silent, odontogenic maxillary sinus mucositis originating from periapical inflammation using MRI: a feasibility study.

OBJECTIVES: Maxillary sinus mucositis is frequently associated with odontogenic foci. Periapical inflammation of maxillary molars and premolars cannot be visualized directly using radiation-based imaging. The purpose of this study was to answer the following clinical question: among patients with periapical inflammatory processes in the maxilla, does the use of magnetic resonance imaging (MRI), as compared to conventional periapical (AP) and panoramic radiography (OPT), improve diagnostic accuracy? METHODS: Forty-two subjects with generalized periodontitis were scanned on a 3 T MRI. Sixteen asymptomatic subjects with mucosal swelling of the maxillary sinus were enrolled in the study. Periapical edema was assessed using short tau inversion recovery (STIR) sequence. Apical osteolysis and mucosal swelling were assessed by MRI, AP, and OPT imaging using the periapical index score (PAI). Comparisons between groups were performed with chi-squared tests with Yates' correction. Significance was set at p < 0.05. RESULTS: Periapical lesions of maxillary premolars and molars were identified in 16 subjects, 21 sinuses, and 58 teeth. Bone edema and PAI scores were significantly higher using MRI as compared to OPT and AP (p < 0.05). Using the STIR sequence, a significant association of PAI score > 1 and the presence of mucosal swelling in the maxillary sinus was detected (p = 0.03). CONCLUSION: Periapical inflammation and maxillary mucositis could be visualized using STIR imaging. The use of MRI may help detect early, subtle inflammatory changes in the periapical tissues surrounding maxillary dentition. Early detection could guide diagnostic criteria, as well as treatment and prevention.

Evaluation of 3D MRI for early detection of bone edema associated with apical periodontitis.

OBJECTIVES: To detect and evaluate early signs of apical periodontitis using MRI based on a 3D short-tau-inversion-recovery (STIR) sequence compared to conventional panoramic radiography (OPT) and periapical radiographs in patients with apical periodontitis. MATERIALS AND METHODS: Patients with clinical evidence of periodontal disease were enrolled prospectively and received OPT as well as MRI of the viscerocranium including a 3D-STIR sequence. The MRI sequences were assessed for the occurrence and extent of bone changes associated with apical periodontitis including bone edema, periradicular cysts, and dental granulomas. OPTs and intraoral periapical radiographs, if available, were assessed for corresponding periapical radiolucencies using the periapical index (PAI). RESULTS: In total, 232 teeth of 37 patients (mean age 62±13.9 years, 18 women) were assessed. In 69 cases reactive bone edema was detected on MRI with corresponding radiolucency according to OPT. In 105 cases edema was detected without corresponding radiolucency on OPT. The overall extent of edema measured on MRI was significantly larger compared to the radiolucency on OPT (mean: STIR 2.4±1.4 mm, dental radiograph 1.3±1.2 mm, OPT 0.8±1.1 mm, P=0.01). The overall PAI score was significantly higher on MRI compared to OPT (mean PAI: STIR 1.9±0.7, dental radiograph 1.3±0.5, OPT 1.2±0.7, P=0.02). CONCLUSION: Early detection and assessment of bone changes of apical periodontitis using MRI was feasible while the extent of bone edema measured on MRI exceeded the radiolucencies measured on OPT. CLINICAL RELEVANCE: In clinical routine, dental MRI might be useful for early detection and assessment of apical periodontitis before irreversible bone loss is detected on conventional panoramic and intraoral periapical radiographs.

Imaging of traumatic mandibular fractures in young adults using CT-like MRI: a feasibility study.

OBJECTIVES: To assess and compare the diagnostic performance of CT-like images based on a three- dimensional (3D) T1-weighted spoiled gradient-echo sequence (3D T1 GRE) with CT in patients with acute traumatic fractures of the mandible. MATERIALS AND METHODS: Subjects with acute mandibular fractures diagnosed on conventional CT were prospectively recruited and received an additional 3 T MRI with a CT-like 3D T1 GRE sequence. The images were assessed by two radiologists with regard to fracture localization, degree of dislocation, and number of fragments. Bone to soft tissue contrast, diagnostic confidence, artifacts, and overall image quality were rated using a five-point Likert-scale. Agreement of measurements was assessed using an independent t-test. RESULTS: Fourteen subjects and 22 fracture sites were included (26 ± 3.9 years; 4 females, 10 males). All traumatic fractures were accurately detected on CT-like MRI (n = 22, κ 1.00 (95% CI 1.00-1.00)). There was no statistically significant difference in the assessment of the fracture dislocation (axial mean difference (MD) 0.06 mm, p = 0.93, coronal MD, 0.08 mm, p = 0.89 and sagittal MD, 0.04 mm, p = 0.96). The agreement for the fracture classification as well as the inter- and intra-rater agreement was excellent (range κ 0.92-0.98 (95% CI 0.96-0.99)). CONCLUSION: Assessment of mandibular fractures was feasible and accurate using CT-like MRI based on a 3D T1 GRE sequence and is comparable to conventional CT. CLINICAL RELEVANCE: For the assessment of acute mandibular fractures, CT-like MRI might become a useful alternative to CT in order to reduce radiation exposure particularly in young patients.

Bornavirus Encephalitis Shows a Characteristic Magnetic Resonance Phenotype in Humans.

OBJECTIVE: The number of diagnosed fatal encephalitis cases in humans caused by the classical Borna disease virus (BoDV-1) has been increasing, ever since it was proved that BoDV-1 can cause human infections. However, awareness of this entity is low, and a specific imaging pattern has not yet been identified. We therefore provide the first comprehensive description of the morphology of human BoDV-1 encephalitis, with histopathological verification of imaging abnormalities. METHODS: In an institutional review board-approved multicenter study, we carried out a retrospective analysis of 55 magnetic resonance imaging (MRI) examinations of 19 patients with confirmed BoDV-1 encephalitis. Fifty brain regions were analyzed systematically (T1w, T2w, T2*w, T1w + Gd, and DWI), in order to discern a specific pattern of inflammation. Histopathological analysis of 25 locations in one patient served as correlation for MRI abnormalities. RESULTS: Baseline imaging, acquired at a mean of 11 ± 10 days after symptom onset, in addition to follow-up scans of 16 patients, revealed characteristic T2 hyperintensities with a predilection for the head of the caudate nucleus, insula, and cortical spread to the limbic system, whereas the occipital lobes and cerebellar hemispheres were unaffected. This gradient was confirmed by histology. Nine patients (47.4%) developed T1 hyperintensities of the basal ganglia, corresponding to accumulated lipid phagocytes on histology and typical for late-stage necrosis. INTERPRETATION: BoDV-1 encephalitis shows a distinct pattern of inflammation in both the early and late stages of the disease. Its appearance can mimic sporadic Creutzfeldt-Jakob disease on MRI and should be considered a differential diagnosis in the case of atypical clinical presentation. ANN NEUROL 2020;88:723-735.

Low-dose MDCT: evaluation of the impact of systematic tube current reduction and sparse sampling on the detection of degenerative spine diseases.

OBJECTIVES: To investigate potential radiation dose reduction for multi-detector computed tomography (MDCT) exams of the spine by using sparse sampling and virtually lowered tube currents combined with statistical iterative reconstruction (SIR). METHODS: MDCT data of 26 patients (68.9 ± 11.7 years, 42.3% males) were retrospectively simulated as if the scans were acquired at 50%, 10%, 5%, and 3% of the original X-ray tube current or number of projections, using SIR for image reconstructions. Two readers performed qualitative image evaluation considering overall image quality, artifacts, and contrast and determined the number and type of degenerative changes. Scoring was compared between readers and virtual low-dose and sparse-sampled MDCT, respectively. RESULTS: Image quality and contrast decreased with virtual lowering of tube current and sparse sampling, but all degenerative changes were correctly detected in MDCT with 50% of tube current as well as MDCT with 50% of projections. Sparse-sampled MDCT with only 10% of initial projections still enabled correct identification of all degenerative changes, in contrast to MDCT with virtual tube current reduction by 90% where non-calcified disc herniations were frequently missed (R1: 23.1%, R2: 21.2% non-diagnosed herniations). The average volumetric CT dose index (CTDIvol) was 1.4 mGy for MDCT with 10% of initial projections, compared with 13.8 mGy for standard-dose imaging. CONCLUSIONS: MDCT with 50% of original tube current or projections using SIR still allowed for accurate diagnosis of degenerative changes. Sparse sampling may be more promising for further radiation dose reductions since no degenerative changes were missed with 10% of initial projections. KEY POINTS: • Most common degenerative changes of the spine can be diagnosed in multi-detector CT with 50% of tube current or number of projections. • Sparse-sampled multi-detector CT with only 10% of initial projections still enables correct identification of degenerative changes, in contrast to imaging with 10% of original tube current. • Sparse sampling may be a promising option for distinct lowering of radiation dose, reducing the CTDIvol from 13.8 to 1.4 mGy in the study cohort.

Magnetic resonance imaging as a diagnostic tool for periodontal disease: A prospective study with correlation to standard clinical findings-Is there added value?

AIM: To evaluate the correlation between standard clinical findings, radiographic (OPT) and magnetic resonance imaging (MRI) as well as to assess whether MRI is capable of providing additional information related to the severity and extent of periodontal disease. METHODS: 42 patients with generalized periodontitis received pre-interventional MRI scans. These were compared to MR images of a periodontal healthy control group (n = 34). The extent of the osseous oedema, detected by MRI, was set in correlation with clinical periodontitis-associated findings. RESULTS: A highly significant correlation between bone oedema and clinical testings such as probing depth (p < 0.0001) and bleeding on probing (p < 0.0001) was revealed. The oedema exceeded the extent of demineralized bone. Patients with a positive BOP test showed a 2.51-fold increase in risk of already having a bone oedema around the respective tooth even if probing depth was ≤3 mm (logistic binary regression analysis, OR 2.51; 95% CI: 1.54-4.11; p < 0.0001). CONCLUSION: MRI findings correlated with standard clinical findings, and MRI was able to depict intraosseous changes before any osseous defect had occurred.

MRI of the inferior alveolar nerve and lingual nerve-anatomical variation and morphometric benchmark values of nerve diameters in healthy subjects.

OBJECTIVE: Since MRI using dedicated imaging sequences has recently shown promising results in direct visualization of the inferior alveolar nerve (IAN) and the lingual nerve (LN) with high spatial resolution, the aim of this study was to generate suitable standard specifications to reliably depict the IAN and LN in MRI and to delineate the anatomy and its variants of these nerves in healthy subjects. METHODS: Thirty healthy volunteers were examined on a 3-T scanner (Elition, Philips Healthcare, Best, the Netherlands). The sequence protocol consisted of 3D STIR, 3D DESS, and 3D T1 FFE "black bone" sequences. RESULTS: The study reconfirmed a good feasibility of direct visualization of proximal and peripheral portions of the IAN and of the proximal course of the LN. The STIR sequence showed the highest apparent signal to noise ratio (aSNR) and best apparent nerve-muscle contrast to noise ratio (aNMCNR) for IAN and for the LN. The applied MRI sequences allowed to differentiate the tissue composition of the neurovascular bundle inside the mandibular canal. CONCLUSION: Dedicated MRI sequence protocols proved effectively to detect the IAN and LN and their course in healthy volunteers. The tissue composition of the mandibular neurovascular bundle was conclusively distinguishable as was the varying topography inside multiple bony channels. CLINICAL RELEVANCE: The presented data on the precise and valid visualization of the IAN and LN have clinical implications in respect to local anesthesia prior to dental treatments in the mandible but also regarding surgical procedures and implant insertion in the molar region.

Comorbidity Assessment in Patients With Oral Squamous Cell Carcinoma: Can Imaging Techniques (Fludeoxyglucose Positron-Emission Tomographic Computed Tomography and Contrast-Enhanced Computed tomography) Provide Additional Information?

PURPOSE: This study evaluated the role of imaging staging examinations (positron-emission tomographic computed tomography [PET/CT] and contrast-enhanced computed tomography [ceCT]) for the assessment of the comorbidity status of patients with oral squamous cell carcinoma (OSCC). A binary null hypothesis was drafted: 1) imaging staging examinations do not augment knowledge about the comorbidity status of patients with OSCC and 2) there is no difference between PET/CT and ceCT in this regard. MATERIALS AND METHODS: A retrospective cohort study design was selected to address the research question. Patients with histologically confirmed OSCC who underwent whole-body staging by PET/CT or ceCT from 2012 through 2015 were considered for inclusion according to predefined criteria. Data collection was performed by the review of patient charts and histology, radiology, and nuclear medicine reports. The Charlson Comorbidity Index (CCI) was chosen to quantify comorbidity and was calculated before and after staging and then compared. The type of imaging staging examination (PET/CT or ceCT) served as the predictor variable and the CCI was determined as the primary outcome variable. Descriptive and inferential statistics were computed for the variable scale. The significance level was set at a P value less than or equal to .05. RESULTS: The sample was composed of 178 patients (71 women, 107 men; average age, 64.2 yr) of whom 109 (61%) underwent PET/CT and 69 (39%) underwent ceCT staging. The pre- and post-staging CCI notably differed. Neither imaging technique showed superior results. CONCLUSION: Relevant and otherwise covert comorbidities can be found by the performance of imaging staging examinations. This enables clinicians to better assess the peri-therapeutic risk and prognosis of patients with OSCC. Therefore, a detailed evaluation of incidental findings on imaging studies is warranted and recommended.

Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica.

OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.

Stimulation frequency determines the distribution of language positive cortical regions during navigated transcranial magnetic brain stimulation.

BACKGROUND: Although language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) gains importance in neuropsychological research and clinical utility, neuroscientists still use different mapping protocols including different stimulation frequencies. To refine the existing language protocol, we tested two different repetition rates of 5 Hz/10 pulses and 7 Hz/10 pulses with a 0 ms delay in 19 healthy subjects. We furthermore investigated differences between both frequencies in case of performance of four different language tasks: object naming, pseudoword reading, verb generation, and action naming. RESULTS: Even the small variance in frequencies revealed statistically significant differences concerning the number and type of language errors. Stimulation with 5 Hz evoked a higher number of all occurred language errors in all language tasks (error rate object naming 14% (5 Hz) vs. 12% (7 Hz); pseudoword reading 4% (5 Hz) vs. 3% (7 Hz); verb generation 13% (5 Hz) vs. 11% (7 Hz); action naming 11% (5 Hz) vs. 9% (7 Hz)), whereas 7 Hz evoked specifically more total speech arrests. CONCLUSION: These findings suggest that the stimulation frequency has to be adapted to the aim of the rTMS language investigation.

Bilateral juvenile osteochondrosis dissecans in monozygotic twins: a case report.

INTRODUCTION: The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully understood. While repetitive physical exercise-related stress is usually assumed to be the main risk factor for the occurrence of OCD, genetic predisposition could have an underestimated influence on the development of the disease. CASE REPORT: We report a case of monozygotic twins with almost identical stages of bilateral osteochondrosis dissecans of the knee joint. In both patients, initially, a unilateral lesion occurred; despite restricted physical exercise, in the further course of the disease a lesion also developed on the contralateral side. While the lesion found most recently demonstrated an ongoing healing process at a 6-month follow-up, the other three lesions showed a natural course of healing under conservative treatment with significant clinical as well as radiological improvements after one year and complete consolidation in magnetic resonance imaging (MRI) after 2 years. CONCLUSION: There could be a genetic component to the development of OCD, although this has not yet been proven. Based on a two-year MRI follow-up, we were able to show the self-limiting characteristics of juvenile osteochondrosis dissecans.

Detection of caries lesions using a water-sensitive STIR sequence in dental MRI.

In clinical practice, diagnosis of suspected carious lesions is verified by using conventional dental radiography (DR), including panoramic radiography (OPT), bitewing imaging, and dental X-ray. The aim of this study was to evaluate the use of magnetic resonance imaging (MRI) for caries visualization. Fourteen patients with clinically suspected carious lesions, verified by standardized dental examination including DR and OPT, were imaged with 3D isotropic T2-weighted STIR (short tau inversion recovery) and T1 FFE Black bone sequences. Intensities of dental caries, hard tissue and pulp were measured and calculated as aSNR (apparent signal to noise ratio) and aHTMCNR (apparent hard tissue to muscle contrast to noise ratio) in both sequences. Imaging findings were then correlated to clinical examination results. In STIR as well as in T1 FFE black bone images, aSNR and aHTMCNR was significantly higher in carious lesions than in healthy hard tissue (p < 0.001). Using water-sensitive STIR sequence allowed for detecting significantly lower aSNR and aHTMCNR in carious teeth compared to healthy teeth (p = 0.01). The use of MRI for the detection of caries is a promising imaging technique that may complement clinical exams and traditional imaging.

Digital planning and individual implants for secondary reconstruction of midfacial deformities: A pilot study.

Objective: To evaluate the feasibility and accuracy of implementing three-dimensional virtual surgical planning (VSP) and subsequent transfer by additive manufactured tools in the secondary reconstruction of residual post-traumatic deformities in the midface. Methods: Patients after secondary reconstruction of post-traumatic midfacial deformities were included in this case series. The metrical deviation between the virtually planned and postoperative position of patient-specific implants (PSI) and bone segments was measured at corresponding reference points. Further information collected included demographic data, post-traumatic symptoms, and type of transfer tools. Results: Eight consecutive patients were enrolled in the study. In five patients, VSP with subsequent manufacturing of combined predrilling/osteotomy guides and PSI was performed. In three patients, osteotomy guides, repositioning guides, and individually prebent plates were used following VSP. The median distances between the virtually planned and the postoperative position of the PSI were 2.01 mm (n = 18) compared to a median distance concerning the bone segments of 3.05 mm (n = 12). In patients where PSI were used, the median displacement of the bone segments was lower (n = 7, median 2.77 mm) than in the group with prebent plates (n = 5, 3.28 mm). Conclusion: This study demonstrated the feasibility of VSP and transfer by additive manufactured tools for the secondary reconstruction of complex residual post-traumatic deformities in the midface. However, the median deviations observed in this case series were unexpectedly high. The use of navigational systems may further improve the level of accuracy.

Faster and Better: How Anomaly Detection Can Accelerate and Improve Reporting of Head Computed Tomography.

BACKGROUND: Most artificial intelligence (AI) systems are restricted to solving a pre-defined task, thus limiting their generalizability to unselected datasets. Anomaly detection relieves this shortfall by flagging all pathologies as deviations from a learned norm. Here, we investigate whether diagnostic accuracy and reporting times can be improved by an anomaly detection tool for head computed tomography (CT), tailored to provide patient-level triage and voxel-based highlighting of pathologies. METHODS: Four neuroradiologists with 1-10 years of experience each investigated a set of 80 routinely acquired head CTs containing 40 normal scans and 40 scans with common pathologies. In a random order, scans were investigated with and without AI-predictions. A 4-week wash-out period between runs was included to prevent a reminiscence effect. Performance metrics for identifying pathologies, reporting times, and subjectively assessed diagnostic confidence were determined for both runs. RESULTS: AI-support significantly increased the share of correctly classified scans (normal/pathological) from 309/320 scans to 317/320 scans (p = 0.0045), with a corresponding sensitivity, specificity, negative- and positive- predictive value of 100%, 98.1%, 98.2% and 100%, respectively. Further, reporting was significantly accelerated with AI-support, as evidenced by the 15.7% reduction in reporting times (65.1 ± 8.9 s vs. 54.9 ± 7.1 s; p < 0.0001). Diagnostic confidence was similar in both runs. CONCLUSION: Our study shows that AI-based triage of CTs can improve the diagnostic accuracy and accelerate reporting for experienced and inexperienced radiologists alike. Through ad hoc identification of normal CTs, anomaly detection promises to guide clinicians towards scans requiring urgent attention.

Geometric accuracy of magnetic resonance imaging-derived virtual 3-dimensional bone surface models of the mandible in comparison to computed tomography and cone beam computed tomography: A porcine cadaver study.

BACKGROUND: Providing accurate 3-dimensional virtual bone surface models is a prerequisite for virtual surgical planning and additive manufacturing in craniomaxillofacial surgery. For this purpose, magnetic resonance imaging (MRI) may be a radiation-free alternative to computed tomography (CT) and cone beam computed tomography (CBCT). PURPOSE: The aim of this study was to assess the geometric accuracy of 3-dimensional T1-weighted MRI-derived virtual bone surface models of the mandible in comparison to CT and CBCT. MATERIALS AND METHODS: Specimens of the mandible from porcine cadavers were scanned with (1) a 3-dimensional T1-weighted MRI sequence (0.6 mm isotropic voxel) optimized for bone imaging, (2) CT, and (3) CBCT. Cortical mandibular structures (n = 10) were segmented using semiautomated and manual techniques. Imaging-based virtual 3-dimensional models were aligned with a high-resolution optical 3-dimensional surface scan of the dissected bone (=ground truth) and global geometric deviations were calculated (mean surface distance [MSD]/root-mean-square distance [RMSD]). Agreement between the imaging modalities was assessed by equivalence testing and Bland-Altman analysis. RESULTS: Intra- and inter-rater agreement was on a high level for all modalities. Global geometric deviations (MSD/RMSD) between optical scans and imaging modalities were 0.225 ± 0.020 mm/0.345 ± 0.074 mm for CT, 0.280 ± 0.067 mm/0.371 ± 0.074 mm for MRI, and 0.352 ± 0.076 mm/0.454 ± 0.071 mm for CBCT. All imaging modalities were statistically equivalent within an equivalence margin of ±0.3 mm, and Bland-Altman analysis indicated high agreement as well. CONCLUSIONS: The results of this study indicate that the accuracy and reliability of MRI-derived virtual 3-dimensional bone surface models is equal to CT and CBCT. MRI may be considered as a reliable alternative to CT and CBCT in computer-assisted craniomaxillofacial surgery.

Accuracy of free-hand positioned patient specific implants (PSI) in primary reconstruction after inferior and/or medial orbital wall fractures.

BACKGROUND: To assess the accuracy with which CAD/CAM-fabricated patient-specific titanium implants (PSI) are positioned for inferior and/or medial orbital wall reconstruction without the use of intraoperative navigation. METHODS: Patients who underwent a primary reconstruction of the orbital walls with PSI due to fractures were enrolled in this retrospective cohort analysis. The primary outcome variables were the mean surface distances (MSD) between virtually planned and postoperative PSI position and single linear deviations in the x-, y- and z-axis at corresponding reference points. Secondary outcome variables included demographic data, classification of orbital wall defects and clinical outcomes. RESULTS: A total of 33 PSI (orbital floor n = 22; medial wall, n = 11) were examined in 27 patients. MSD was on a comparable level for the orbital floor and medial wall (median 0.39 mm, range 0.22-1.53 mm vs. median 0.42 mm, range 0.21-0.98 mm; p = 0.56). Single linear deviations were lower for reconstructions of the orbital floor compared to the medial wall (median 0.45 vs. 0.79 mm; p < 0.05). There was no association between the occurrence of diplopia and the accuracy level (p = 0.418). CONCLUSIONS: Free-hand positioning of PSI reaches a clinically appropriate level of accuracy, limiting the necessity of navigational systems to selected cases.

Prediction of surface area size in orbital floor and medial orbital wall fractures based on topographical subregions.

OBJECTIVE: This retrospective study evaluates the occurrence and frequency of different fracture patterns in a series of computed tomography (CT) scans in terms of the AOCMF Trauma Classification (TC) orbit module and correlates the assigned defects with measurements of the fracture area in order to get an approximate guideline for fracture size predictions on the basis of the classification. MATERIAL AND METHODS: CT scans of patients with orbital floor fractures were evaluated using the AOCMFTC to determine the topographical subregions. The coding consisted of: W = orbital wall, 1 = anterior orbit, 2 = midorbit, i = inferior, m = medial. The 3-dimensional surface area size of the fractures was quantified by the "defect body" method (Brainlab, Munich, Germany). The fracture area size and its confidence and prediction interval within each topographical subregion was estimated by regression analysis. RESULTS: A total of 137 CT scans exhibited 145 orbital floor fractures, which were combined with 34 medial orbital wall fractures in 31 patients. The floor fractures - W1(i)2(i) (n = 86) and W1(i) (n = 19) were the most frequent patterns. Combined floor and medial wall fractures most frequently corresponded to the pattern W1 (im)2 (im) (n = 15) ahead of W1 (im) 2(i) (n = 10). The surface area size ranged from 0.11 cm2 to 6.09 cm2 for orbital floor and from 0.29 cm2 to 5.43 cm2 for medial wall fractures. The prediction values of the mean fracture area size within the subregions were computed as follows: W1(i) = 2.25 cm2, W2(i) = 1.64 cm2, W1(i)2(i) = 3.10 cm2, W1(m) = 1.36 cm2, W2(m) = 1.65 cm2, W1(m)2(m) = 2.98 cm2, W1 (im) = 3.35 cm2, W1 (im) 2(i) = 4.63 cm2, W1 (im)2(m) = 4.06 cm2 and W1 (im)2 (im) = 7.16 cm2. CONCLUSION: The AOCMFTC orbital module offers a suitable framework for topographical allocation of fracture patterns inside the infero-medial orbital cavity. The involvement of the subregions is of predictive value providing estimations of the mean 3-D fracture area size.

Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases.

OBJECTIVE: To analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases. METHODS: Retrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating disease, and healthy controls with MOG alpha-1-IgG positive (n = 202) or negative serostatus (n = 176). Samples were analyzed for their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG Ig domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from multiple species using live cell-based, tissue immunofluorescence assays and ELISA. RESULTS: The strongest IgG reactivities were directed against the longest MOG isoforms alpha-1 (the currently used standard test for MOG-IgG) and beta-1, whereas the other isoforms were less frequently recognized. Using principal component analysis, we identified 3 different binding patterns associated with non-MS disease: (1) isolated reactivity to MOG-alpha-1/beta-1 (n = 73), (2) binding to MOG-alpha-1/beta-1 and at least one other alpha, but no beta isoform (n = 64), and (3) reactivity to all 6 MOG isoforms (n = 65). The remaining samples were negative (n = 176) for MOG-IgG. These MOG isoform binding patterns were associated with a non-MS demyelinating disease, but there were no differences in clinical phenotypes or disease course. The 3 MOG isoform patterns had distinct immunologic characteristics such as differential binding to soluble MOG-ecIgD, sensitivity to MOG mutations, and binding to human MOG in ELISA. CONCLUSIONS: The novel finding of differential MOG isoform binding patterns could inform future studies on the refinement of MOG-IgG assays and the pathophysiologic role of MOG-IgG.