Assessing the Performance of Artificial Intelligence Models: Insights from the American Society of Functional Neuroradiology Artificial Intelligence Competition.

BACKGROUND AND PURPOSE: Artificial intelligence (AI) models in radiology are frequently developed and validated using datasets from a single institution and are rarely tested on independent, external datasets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multi-center AI competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency. MATERIALS AND METHODS: In total, 1201 anonymized, full-head NCCT clinical scans from five institutions were pooled to form the dataset. The dataset encompassed normal studies as well as pathologies including acute ischemic stroke, intracranial hemorrhage, traumatic brain injury, and mass effect (detection of these-task 1). NCCTs were also assessed to determine if findings were consistent with expected brain changes for the patient's age (task 2: age-based normality assessment) and to identify any abnormalities requiring immediate medical attention (task 3: evaluation of findings for urgent intervention). Five neuroradiologists labeled each NCCT, with consensus interpretations serving as the ground truth. The competition was announced online, inviting academic institutions and companies. Independent central analysis assessed each model's performance. Accuracy, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were generated for each AI model, along with the area under the ROC curve (AUROC). RESULTS: 1177 studies were processed by four teams. The median age of patients was 62, with an interquartile range of 33. 19 teams from various academic institutions registered for the competition. Of these, four teams submitted their final results. No commercial entities participated in the competition. For task 1, AUROCs ranged from 0.49 to 0.59. For task 2, two teams completed the task with AUROC values of 0.57 and 0.52. For task 3, teams had little to no agreement with the ground truth. CONCLUSIONS: To assess the performance of AI models in real-world clinical scenarios, we analyzed their performance in the ASFNR AI Competition. The first ASFNR Competition underscored the gap between expectation and reality; the models largely fell short in their assessments. As the integration of AI tools into clinical workflows increases, neuroradiologists must carefully recognize the capabilities, constraints, and consistency of these technologies. Before institutions adopt these algorithms, thorough validation is essential to ensure acceptable levels of performance in clinical settings.ABBREVIATIONS: AI = artificial intelligence; ASFNR = American Society of Functional Neuroradiology; AUROC = area under the receiver operating characteristic curve; DICOM = Digital Imaging and Communications in Medicine; GEE = generalized estimation equation; IQR = interquartile range; NPV = negative predictive value; PPV = positive predictive value; ROC = receiver operating characteristic; TBI = traumatic brain injury.

Long-term outcomes of hospitalized patients with SARS-CoV-2/COVID-19 with and without neurological involvement: 3-year follow-up assessment.

BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.

Cognitive inflexibility and heightened error monitoring are related to lower sexual functioning.

Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research.

Lysosomal processing of sulfatide analogs alters target NKT cell specificity and immune responses in cancer.

In a structure-function study of sulfatides that typically stimulate type II NKT cells, we made an unexpected discovery. We compared analogs with sphingosine or phytosphingosine chains and 24-carbon acyl chains with 0-1-2 double bonds (C or pC24:0, 24:1, or 24:2). C24:1 and C24:2 sulfatide presented by the CD1d monomer on plastic stimulated type II, not type I, NKT cell hybridomas, as expected. Unexpectedly, when presented by bone marrow-derived DCs (BMDCs), C24:2 reversed specificity to stimulate type I, not type II, NKT cell hybridomas, mimicking the corresponding ß-galactosylceramide (ßGalCer) without sulfate. C24:2 induced IFN-γ-dependent immunoprotection against CT26 colon cancer lung metastases, skewed the cytokine profile, and activated conventional DC subset 1 cells (cDC1s). This was abrogated by blocking lysosomal processing with bafilomycin A1, or by sulfite blocking of arylsulfatase or deletion of this enyzme that cleaves off sulfate. Thus, C24:2 was unexpectedly processed in BMDCs from a type II to a type I NKT cell-stimulating ligand, promoting tumor immunity. We believe this is the first discovery showing that antigen processing of glycosylceramides alters the specificity for the target cell, reversing the glycolipid's function from stimulating type II NKT cells to stimulating type I NKT cells, thereby introducing protective functional activity in cancer. We also believe our study uncovers a new role for antigen processing that does not involve MHC loading but rather alteration of which type of cell is responding.

Elaborating and Testing Erotic Target Identity Inversion Theory in Three Paraphilic Samples.

Some men sexually attracted to types of persons (e.g., women) or things (e.g., animals) also have internalized sexual attractions: sexual arousal by the idea of being the type of person or thing to whom they are attracted. Consequently, some of these men develop erotic target identity inversions, in which they imitate, yearn to be, or identify as an instance of their erotic target. Erotic Target Identity Inversion Theory predicts that for every external erotic target to which men are attracted, a subset of men will develop an internalized sexual attraction, which may cause an erotic target identity inversion. We examined these predictions in Internet surveys of three samples of men with paraphilic sexual interests: 322 men attracted to amputees, 1501 men attracted to animals, and 402 men attracted to severely obese persons. All samples included substantial minorities of men reporting internalized sexual attractions and erotic target identity inversions specific to their external sexual attractions (e.g., men attracted to amputees who are also aroused by the fantasy of being amputees and wish to become amputees). The correlation between degree of each internalized sexual attraction and degree of its corresponding erotic target identity inversion was approximately 1.0 after correction for attenuation. In each sample, participants' specific internalized sexual attraction was positively correlated with autogynephilia, likely the most common internalized sexual attraction in men. Erotic Target Identity Inversion Theory can potentially explain a variety of otherwise puzzling phenomena, including transgender identity among female-attracted natal males and men seeking amputations of healthy limbs.

High-Grade Ectopic Pituitary Adenoma within the Cerebellopontine Angle: A Case Report.

Ectopic pituitary tumors are neoplasms with no connection to the pituitary gland and are commonly deposited in other areas of the anterior skull base. A 32-year-old woman presented with a 3-month history of right-sided facial weakness, sensorineural hearing loss, diplopia, and severe headaches. Physical examination revealed a mid-dilated sluggishly reactive right pupil with slight limitation in all gazes, as well as right-sided orbicularis weakness, lagophthalmos, and decreased facial sensation. A magnetic resonance imaging (MRI) of the head without contrast revealed a 3.7 × 1.8 × 2.6 cm mildly enhancing mass in the right internal acoustic meatus and along the petrous ridge. The case was brought before the institution's tumor board, where concern for higher grade pathology, such as hemangiopericytoma, was discussed. Per patient preference, surgical biopsy of the tumor was performed. Immunohistochemical staining revealed a World Health Organization (WHO) grade II neuroendocrine tumor, with cells staining positive for synaptophysin, chromogranin, and CD56, with a K i -67 index of 8%. In addition to the ectopic location, this pituitary tumor was noted to be aggressive in nature based on its high K i -67 index. Surgical excision and radiologic therapy of tumors involving the CPA are appropriate treatments in most cases.

Sexual Orientation, Sexual Motivation, and Erotic Target Identity Inversions in Male Adult Baby/Diaper Lovers.

Adult baby/diaper lovers (AB/DLs) enjoy role-playing as babies and/or wearing diapers. They also engage in other related activities, such as urinating or defecating themselves and having an adult care for them. Previous surveys have revealed that AB/DLs commonly report sexual motivation, a finding that is corroborated by case reports in the psychiatric literature and some media interviews. The fact that AB/DLs change their appearance and behavior to become more like babies raises the possibility that they have an erotic target identity inversion (ETII). In ETIIs, a person's external erotic target is inverted into the self, resulting in sexual arousal by the fantasy of being a member of the target class or by imitating one. If AB/DLs are sexually motivated by an ETII, they should experience both sexual attraction to babies and sexual arousal by the fantasy of being a baby. We surveyed 207 male AB/DLs recruited from the Internet about their sexual orientation, sexual motivation, and sexual interests for a primarily quantitative analysis. Consistent with past research, a substantial minority of participants reported non-heterosexual identities (42%), and a large majority reported some degree of sexual motivation for being AB/DLs (93%). Wearing diapers and urinating or defecating oneself were rated as especially sexual. Even though 40% of participants reported sexual arousal by the fantasy of being a baby, only 4% reported sexual attraction to babies. This pattern of results is contrary to predictions from the concept of ETIIs. Instead, participants indicated that physical or mental pain, humiliation, and an adult woman were important to their sexual fantasies of being a baby. Masochism appears to be a promising alternative to an ETII for explaining the sexual motivation of AB/DLs.

Impact of magnetic resonance angiography parameters on stroke prevention therapy in pediatric patients with sickle cell anemia.

BACKGROUND: Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which has significant risks. Flow artifact, intrinsic to magnetic resonance angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol for patients with SCA. METHODS: A standardized MRA scanning protocol with an echo time of less than 5 ms was implemented at Montefiore Medical Center (MMC), NY in May 2016. Retrospective chart review identified 21 pediatric patients with SCA, with an MRA head both pre- and post-May 2016. Arterial stenosis on MRA, machine parameters, and treatment plans were compared pre- and post-implementation. RESULTS: Ten of the 21 patients met inclusion criteria. Previously seen stenosis was re-classified to a lower degree in six of the 10 patients, leading to discontinuation of transfusions in five patients. No patients required escalation of therapy to chronic transfusions. CONCLUSION: Optimizing flow artifact by decreasing echo time to less than 5 ms can improve accurate interpretation of cerebrovascular disease, and ensure appropriate treatment plans are in place for stroke prevention. This is especially important for implementing "TCD With Transfusions Changing to Hydroxyurea (TWiTCH)" clinical trial results in the real-world setting.

Imaging score for differentiation of meningioma grade.

PURPOSE: We sought to establish a comprehensive imaging score indicating the likelihood of higher WHO grade meningiomas pre-operatively. METHODS: All surgical intracranial meningioma patients at our institution between 2014 and 2018 underwent retrospective chart review. Preoperative MRI sequences were reviewed, and imaging features were included in the score based on statistical and clinical significance. Point values for each significant feature were assigned based on the beta coefficients obtained from multivariate analysis. The imaging score was calculated by adding up the points, for a total score of 0 to 5. The predictive ability of the score to identify higher-grade meningiomas was evaluated. RESULTS: Ninety patients, 50% of whom had a postoperative diagnosis of WHO grade II meningioma, were included. The mean age for the population was 59.9 years and 70% were female. Tumor volume ≥ 36.0 cc was assigned 2 points, presence of irregular tumor borders was assigned 2 points, and presence of peritumoral edema was assigned 1 point. The probability of having a WHO grade II meningioma was 0% with a score of 0, 25.0% with a score of 1, 38.5% with a score of 2, 65.4% with a score of 3, and 83.3% with a score of 4 or greater. A threshold of ≥ 3 points achieved a recall of 0.80, precision of 0.73, F1-score of 0.77, accuracy of 0.76, and AUC of 0.82. CONCLUSION: The proposed imaging scoring system had good predictive capability for WHO grade II meningiomas with good discrimination and calibration. External validation is needed.

A nine-month-old boy with regression of milestones and severe constipation: an unusual case of a large spinal NTRK1 fusion pilocytic astrocytoma.

INTRODUCTION: Pilocytic astrocytoma, a World Health Organization grade 1 tumor, is the most common brain tumor in children between 5 and 14 years of age and the second most common in children younger than 5 and older than 14. Although classical to the cerebellum and hypothalamic regions, it can also arise in the spinal cord. Larotrectinib, a selective inhibitor of tropomyosin receptor kinase, has been effective in pediatric tumors with NTRK fusion mutations in children as young as 1-month-old. CASE: We share the case of a 9-month-old boy who presented with a 4-month history of regression of his milestones and severe constipation who was found to have a large spinal pilocytic astrocytoma with multiple intracranial periventricular lesions.

Bilateral cranial nerve 6 palsy in a patient with multiple sclerosis and vitamin D-dependent rickets.

The development of multiple sclerosis (MS) is multifactorial. Elevated levels of vitamin D may lower the risk and reduce relapses by immunomodulatory mechanisms. Conversely, vitamin D-dependent rickets (VDDR), an inheritable form of rickets secondary to impairment in vitamin D synthesis or action, may increase MS risk. This has been described in three patients with VDDR type 1A. Here, we present a patient with VDDR type 2 - unclear if type 2A or 2B based on historical genetic testing - who subsequently developed MS. She presented with 8 weeks of binocular horizontal diplopia and was found to have 8 prism dioptres of esotropia in primary gaze and a mild limitation of abduction in both eyes. Radiological workup was consistent with MS demyelination. She was started on solumedrol infusions, with full resolution of the esotropia and abduction deficits. She has since been transitioned to ocrelizumab with vitamin D supplementation and has not had a relapse to date. It is important to consider MS in patients genetically predisposed to low vitamin D levels or functional impairment, as with VDDR. Vitamin D supplementation can achieve remission in some forms of VDDR, and its role in MS prevention in these patients should be considered. In patients with type 2A or 2B VDDR, who have impairment in receptor function, additional treatment modalities require investigation. Lastly, demyelination is a rare cause of bilateral cranial nerve 6 palsy. This case illustrates the importance of considering MS in cranial nerve palsies, particularly in patients with vitamin D deficiencies or functional impairment.

How Autogynephilic Are Natal Females?

Blanchard proposed that autogynephilia is a natal male's paraphilic sexual arousal in response to the thought or fantasy of being a woman. Furthermore, based on evidence collected from natal males with gender dysphoria, Blanchard argued that autogynephilia is the fundamental motivation among nonhomosexual males (i.e., those not exclusively attracted to men) who pursue sex reassignment surgery or live as transgender women. These ideas have been challenged by several writers who have asserted, or offered evidence, that autogynephilia is common among women. However, their evidence was weakened by problematic measures and limited comparison groups. We compared four samples of autogynephilic natal males (N = 1549), four samples of non-autogynephilic natal males (N = 1339), and two samples of natal females (N = 500), using Blanchard's original measure: the Core Autogynephilia Scale. The autogynephilic samples had much higher mean scores compared with non-autogynephilic natal males and natal females, who were similar. Our findings refute the contention that autogynephilia is common among natal females.

Lyme Neuroborreliosis Presenting as Multiple Cranial Neuropathies.

Neuroborreliosis can manifest with cranial nerve (CN) palsies, commonly CN VII. Rarely have isolated or multiple palsies been reported. We describe a case of a young female from a Lyme endemic region who presented with bilateral CN VI palsies and a dilated right pupil, possibly a partial CN III palsy. She later developed CN VII palsy and bilateral enhancement of multiple cranial nerves on neuroimaging. She was diagnosed with Lyme disease by serological testing, with gradual improvement on antibiotics. Our case illustrates that neuroborreliosis can present as any or multiple CN palsies, and should be considered particularly in endemic areas.

COVID-19 Patients in the COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx.

Background: Early in the pandemic, we established COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx and implemented a detailed evaluation protocol to assess physical, emotional, and cognitive function, pulmonary function tests, and imaging for COVID-19 survivors. Here, we report our findings up to five months post-acute COVID-19. Methods: Main outcomes and measures included pulmonary function tests, imaging tests, and a battery of symptom, physical, emotional, and cognitive assessments 5 months post-acute COVID-19. Findings: Dyspnea, fatigue, decreased exercise tolerance, brain fog, and shortness of breath were the most common symptoms but there were generally no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Many patients had abnormal physical, emotional, and cognitive scores, but most functioned independently; there were no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Six-minute walk tests, lung ultrasound, and diaphragm excursion were abnormal but only in the hospitalized cohort. Pulmonary function tests showed moderately restrictive pulmonary function only in the hospitalized cohort but no obstructive pulmonary function. Newly detected major neurological events, microvascular disease, atrophy, and white-matter changes were rare, but lung opacity and fibrosis-like findings were common after acute COVID-19. Interpretation: Many COVID-19 survivors experienced moderately restrictive pulmonary function, and significant symptoms across the physical, emotional, and cognitive health domains. Newly detected brain imaging abnormalities were rare, but lung imaging abnormalities were common. This study provides insights into post-acute sequelae following SARS-CoV-2 infection in neurological and pulmonary systems which may be used to support at-risk patients and develop effective screening methods and interventions.

Review of COVID-19, part 2: Musculoskeletal and neuroimaging manifestations including vascular involvement of the aorta and extremities.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world resulting in severe morbidity, mortality and economic hardship, altering the landscape of healthcare forever. Its devastating and most frequent thoracic and cardiac manifestations have been well reported since the start of the pandemic. Its extra-thoracic manifestations are myriad and understanding them is critical in diagnosis and disease management. The role of radiology is growing in the second wave and second year of the pandemic as the multiorgan manifestations of COVID-19 continue to unfold. Musculoskeletal, neurologic and vascular disease processes account for a significant number of COVID-19 complications and understanding their frequency, clinical sequelae and imaging manifestations is vital in guiding management and improving overall survival. The authors aim to provide a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19. In Part I, abdominal manifestations of COVID-19 in adults and multisystem inflammatory syndrome in children will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Racial preferences in sexual attraction among White heterosexual and gay men: Evidence from sexual arousal patterns and negative racial attitudes.

Racial preferences in sexual attraction are highly visible and controversial. They may also negatively impact those who are excluded. It is unclear whether these preferences are merely self-attributed or extend to patterns of experienced sexual arousal. Furthermore, some argue that racial preferences in sexual attraction reflect idiosyncratic personal preferences, while others argue that they are more systematically motivated and reflect broader negative attitudes toward particular races. In two studies, we examined these issues by measuring the sexual arousal patterns and negative racial attitudes of 78 White men in relation to their racial preferences in sexual attraction to White versus Black people. For both White heterosexual men (n = 40; Study 1) and White gay men (n = 38; Study 2), greater racial preferences in sexual attraction to White versus Black people of their preferred gender were associated with more subjective and genital arousal by erotic stimuli featuring White versus Black people of their preferred gender, and with more explicit and implicit negative attitudes toward Black people. Findings suggest that racial preferences in sexual attraction are reflected in patterns of sexual arousal, and they might also be systematically motivated by negative attitudes toward particular races.

Review of COVID-19, part 1: Abdominal manifestations in adults and multisystem inflammatory syndrome in children.

The coronavirus disease 2019 (COVID -19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world, resulting in severe morbidity, mortality and economic hardship, and altering the landscape of healthcare forever. Although primarily a pulmonary illness, it can affect multiple organ systems throughout the body, sometimes with devastating complications and long-term sequelae. As we move into the second year of this pandemic, a better understanding of the pathophysiology of the virus and the varied imaging findings of COVID-19 in the involved organs is crucial to better manage this complex multi-organ disease and to help improve overall survival. This manuscript provides a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and features of MIS-C will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.