Efficacy of denosumab monotherapy among adults with Langerhans cell histiocytosis: A prospective clinical trial.

This phase IIb clinical trial evaluated the efficacy of a bimonthly treatment schedule (Q8W) with 4 subcutaneous doses of denosumab 120 mg among adults with Langerhans cell histiocytosis needing first-line systemic therapy for either multifocal single-system disease or multisystem disease without risk organ involvement. Two months after the last treatment administration, seven patients showed disease regression, one stable disease, one non-active disease, and one disease progression. One year after treatment, progression was evident in two patients, while the remaining exhibited either a regression (three patients) or non-active disease (five patients). No permanent sequalae developed during the study and no adverse events were adjudicated in treatment. In conclusion, four doses of denosumab 120 mg Q8W subcutaneously are an effective treatment option in Langerhans cell histiocytosis patients without risk organ involvement exhibiting a response rate of 80%. Further studies are needed to confirm its role as a disease modifying agent.

Radiomics/Radiogenomics in Lung Cancer: Basic Principles and Initial Clinical Results.

Lung cancer is the leading cause of cancer-related deaths worldwide, and elucidation of its complicated pathobiology has been traditionally targeted by studies incorporating genomic as well other high-throughput approaches. Recently, a collection of methods used for cancer imaging, supplemented by quantitative aspects leading towards imaging biomarker assessment termed "radiomics", has introduced a novel dimension in cancer research. Integration of genomics and radiomics approaches, where identifying the biological basis of imaging phenotypes is feasible due to the establishment of associations between molecular features at the genomic-transcriptomic-proteomic level and radiological features, has recently emerged termed radiogenomics. This review article aims to briefly describe the main aspects of radiogenomics, while discussing its basic limitations related to lung cancer clinical applications for clinicians, researchers and patients.

A few-shot U-Net deep learning model for lung cancer lesion segmentation via PET/CT imaging.

Over the past few years, positron emission tomography/computed tomography (PET/CT) imaging for computer-aided diagnosis has received increasing attention. Supervised deep learning architectures are usually employed for the detection of abnormalities, with anatomical localization, especially in the case of CT scans. However, the main limitations of the supervised learning paradigm include (i) large amounts of data required for model training, and (ii) the assumption of fixed network weights upon training completion, implying that the performance of the model cannot be further improved after training. In order to overcome these limitations, we apply a few-shot learning (FSL) scheme. Contrary to traditional deep learning practices, in FSL the model is provided with less data during training. The model then utilizes end-user feedback after training to constantly improve its performance. We integrate FSL in a U-Net architecture for lung cancer lesion segmentation on PET/CT scans, allowing for dynamic model weight fine-tuning and resulting in an online supervised learning scheme. Constant online readjustments of the model weights according to the users' feedback, increase the detection and classification accuracy, especially in cases where low detection performance is encountered. Our proposed method is validated on the Lung-PET-CT-DX TCIA database. PET/CT scans from 87 patients were included in the dataset and were acquired 60 minutes after intravenous18F-FDG injection. Experimental results indicate the superiority of our approach compared to other state-of-the-art methods.

Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis.

The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27-10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48-4.04 and HR:2.25; 95% CIs:1.55-3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

A Longitudinal Study of Alterations of S100B, sRAGE and Fas Ligand in Association to Olanzapine Medication in a Sample of First Episode Patients with Schizophrenia.

BACKGROUND & OBJECTIVE: Neuroinflammation has been proposed as a major mechanism in schizophrenic disorder. Specifically, an increase in the inflammatory response in the central nervous system is capable of activating microglial cells, leading to the release of pro-inflammatory cytokines and thus activating apoptotic signaling. An increase in apoptosis may underlie a potential role of immune neuropathology in the etiopathogenesis of schizophrenia and specifically, the onset of the disorder. We analyzed in whole blood, levels of S100B, the receptor for advanced glycation end products (RAGE) and the apoptotic marker Fas Ligand in a sample of 13 first episode of schizophrenia twice at baseline before the initiation of any antipsychotic medication (A) and 6 weeks later following an antipsychotic monotherapy with olanzapine (B) and in a sample of 10 healthy controls. The S100B, RAGE and Fas Ligand showed statistically significant differences before and after treatment; the S100B measurements yielded a p-value of 0.004 while the soluble RAGE and Fas Ligand measurements yielded a p=0.03, and p=0.04 respectively. The differences between cases and controls were not statistically significant for all measurements, with the only exception being the S100B values where both samples A and B showed significantly higher values than the controls with p=8.5x10-8 and p=2.9x10-10 respectively. CONCLUSION: The levels of S100B, RAGE, and Fas Ligand of drug-naive first episode psychosis patients with schizophrenia were significantly higher than that of the same medicated first episode psychosis patients, indicating that an increase of apoptotic signaling is present at the onset of schizophrenia and is also associated with treatment progress.

The effect of patient anxiety and depression on motion during myocardial perfusion SPECT imaging.

BACKGROUND: Patient motion during myocardial perfusion SPECT imaging (MPI) may be triggered by a patient's physical and/or psychological discomfort. The aim of this study was to investigate the impact of state anxiety (patient's reaction to exam-related stress), trait anxiety (patient's personality characteristic) and depression on patient motion during MPI. METHODS: All patients that underwent MPI in our department in a six-month period were prospectively enrolled. One hundred eighty-three patients (45 females; 138 males) filled in the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI), along with a short questionnaire regarding their age, height and weight, level of education in years, occupation, and marital status. Cardiovascular and other co-morbidity factors were also evaluated. Through inspection of raw data on cinematic display, the presence or absence of patient motion was registered and classified into mild, moderate and severe, for both phases involved in image acquisition. RESULTS: The correlation of patient motion in the stress and delay phases of MPI and each of the other variables was investigated and the corresponding Pearson's coefficients of association were calculated. The anxiety-motion (r = 0.43, P < 0.0001) and depression-motion (r = 0.32, P < 0.0001) correlation results were moderately strong and statistically significant for the female but not the male patients. All the other variables did not demonstrate any association with motion in MPI, except a weak correlation between age and motion in females (r = 0.23, P < 0.001). CONCLUSIONS: The relationship between anxiety-motion and depression-motion identified in female patients represents the first supporting evidence of psychological discomfort as predisposing factor for patient motion during MPI.

Education, training, and professional issues of radiographers in six European countries: a comparative review.

Radiographers constitute an important part of a multidisciplinary radiation-based imaging and therapy chain. However, is there a common framework for assuring high education, training, and subsequent practice of profession among European countries? A study was conducted, based on a questionnaire that consisted of three parts, concerning education and training (Part A), national registry (Part B), and professional issues (Part C). Analysis of the collected data suggested that a common policy is generally followed in the countries investigated; however, differences were not negligible. A common framework of educational programmes among European countries could form the basis for overall standardisation at national and international level.

Differentiating between Traumatic Pathology and Congenital Variant: A Case Report of Butterfly Vertebra.

Butterfly vertebra is a rare congenital malformation of the spine, which is usually reported in the literature as an isolated finding. We describe a 40-year-old woman that presented to our emergency department with back pain and sciatica. Initial radiological evaluation revealed an incidental finding of a L4 butterfly vertebra in the anteroposterior and lateral view radiographs. The patient presented with no neurological deficit. This rare congenital anomaly is usually asymptomatic, and awareness of its non-traumatic nature is critical in order to establish a correct diagnosis. Further evaluation of the patient is necessary to exclude pathologic fracture, infection, or associated vertebral anomalies and syndromes, such as Alagille, Jarcho-Levin, Crouzon, and Pfeiffer syndromes. Furthermore, in the emergency setting, awareness of this entity is needed so that a correct diagnosis can be established.

Lymphatic Path of the Inguinal Lymph Node Metastases in Anorectal Cancer: The Springbok Pattern.

Sentinel lymph node biopsy has been established as a feasible and effective method for defining the inguinal node status in patients with anal adenocarcinoma exceeding the dentate line. We present the axial lymphoscintigraphic image that depicts thoroughly the injection site around the anus, the lymphatic path, and the inguinal sentinel lymph nodes, bilaterally. The distinct springbok pattern was named after the unique horn shape of the African gazelle. This image puts on the map the anoinguinal lymphatic path and highlights the need for complete inguinal lymph node and related lymphatic path dissection in metastatic anal cancer.

Recurrent thyroid cancer diagnosis: ROC study of the effect of a high-resolution head and neck 18F-FDG PET/CT scan.

RATIONALE AND OBJECTIVES: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has demonstrated significant value in the evaluation of patients with indication of recurrent thyroid cancer with negative conventional workup. The hypothesis of this study was that the addition of a dedicated, high-resolution head and neck scan (HNS) to the standard whole-body scan (WBS) improves the accuracy of the detection and diagnosis of recurrent thyroid cancer. MATERIALS AND METHODS: Forty-three consecutive patients suspected for recurrent thyroid cancer, as indicated by increased tumor markers, prospectively underwent a WBS and a HNS with (18)F-FDG PET/CT. The patients were followed up to establish ground truth. A receiver operator characteristic (ROC) study with two observers was conducted to evaluate the impact of the additional HNS on the detection and diagnosis of recurrent thyroid cancer. Indices of performance included the area under the ROC curve (AUC), the number of detected abnormal foci, and the size of the detected foci without and with the HNS images. RESULTS: ROC results showed that the addition of the HNS to the standard WBS increased the average AUC index of performance from 0.69 to 0.96, a statistically significant difference with a confidence interval (CI) of -0.33 to -0.19. Diagnosis was also improved with the average AUC increasing from 0.79 to 0.87 but differences were not statistically significant (CI, -0.19 to 0.04). Interreader agreement was "good" in the detection task and "excellent" in the diagnostic task. The addition of the HNS increased the number of detected foci in the positive patients by an average of 37%, whereas false-positive detections in the negative patients increased by an average of 10%. Reported average maximum lesion size also increased with the HNS addition by an average of 11%. CONCLUSIONS: The addition of a high-resolution HNS to the standard whole-body PET/CT imaging improves readers' performance in the detection and diagnosis of recurrent thyroid cancer and could greatly benefit patient care.

The role of multimodality imaging in the evaluation of Takayasu arteritis.

OBJECTIVES: Takayasu arteritis is a rare large vessel vasculitis of unknown etiology, in which both early diagnosis and follow-up present very significant challenges. The high incidence of disease-associated morbidity and significant risk of premature death-particularly in young adults-mandate the need to facilitate early diagnosis and aggressive treatment where appropriate. The aim of this review is to summarize the current level of knowledge regarding the usefulness of evolving imaging modalities in the diagnostic workup and management of patients suffering with Takayasu arteritis. We also propose an imaging algorithm for the evaluation of this population. METHODS: A MEDLINE search for articles published between January 1999 and December 2011 was conducted using the following keywords: Takayasu arteritis, imaging modalities, echocardiogram, cardiac magnetic resonance, positron emission tomography scan, diagnosis. RESULTS: Imaging studies-particularly cardiac magnetic resonance-can assist early diagnosis by demonstrating vascular lesions even when angiography is negative, by identifying the presence of vascular inflammation and/or wall thickening; they are also useful for monitoring purposes. However, availability, expertise, high cost, and radiation are considerable limitations. Magnetic resonance imaging, although it can detect both anatomic and pathophysiologic changes without radiation, is time-consuming, needs high expertise, and still remains an expensive tool, not widely available. CONCLUSIONS: Knowledge of the advantages and limitations of the various imaging procedures can complement the physicians' clinical assessment and, along with nonspecific serologic tests, can aid them in diagnosing active arteritis and commence relevant treatment early on, as well as monitor activity and tailor therapy subsequently.

Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty.

BACKGROUND CONTEXT: Over the past 20 years, methods of minimally invasive surgery have been developed for the treatment of vertebral compression fractures. Balloon kyphoplasty and vertebroplasty are associated with a recurrent fracture risk in the adjacent levels after the surgical procedure. In certain patient categories with impaired bone metabolism, the risk of subsequent fractures after kyphoplasty is increased. PURPOSE: To determine the incidence of recurrent fractures after kyphoplasty and explore whether the status of bone metabolism and 25-hydroxyvitamin D (25(OH)D) levels affect the occurrence of these fractures. STUDY DESIGN: Prospective longitudinal clinical study. PATIENT SAMPLE: Forty female postmenopausal women with primary osteoporosis and acute symptomatic vertebral compression fractures. OUTCOME MEASURES: Identification of new vertebral fractures and documentation of indicators of bone metabolism. METHODS: A total of ninety-eight kyphoplasties were performed in 40 female patients. Balloon kyphoplasty was performed on all symptomatic acute vertebral compression fractures. Age, body mass index, history of tobacco use, number of initial vertebral fractures, intradiscal cement leakage, history of nonspinal fractures, use of antiosteoporotic medications, bone mineral density, bone turnover markers, and 25(OH)D levels were assessed. All participants were evaluated clinically and/or radiographically. Follow-up period was 18 months. RESULTS: The mean population age was 70.6 years (range, 40-83 years). After initial kyphoplasty procedure, nine patients (11 levels) (22.5% of patients; 11.2% of levels) developed a postkyphoplasty vertebral compression fracture. Cement leakage was identified in seven patients (17.5%). The patients without recurrent fractures after kyphoplasty demonstrated higher levels of 25(OH)D (22.6±5.51 vs. 14.39±7.47; p=.001) and lower N-terminal cross-linked telopeptide values (17.11±10.20 vs. 12.90±4.05; p=.067) compared with the patients with recurrent fractures. CONCLUSIONS: Bone metabolism and 25(OH)D levels seem to play a role in the occurrence of postkyphoplasty recurrent vertebral compression fractures.

Can pain influence the severity of findings of an (18)F-FDG PET/CT scan in loosening hip arthroplasty?

Pain is a common symptom after loosening and/or after infection of arthroplasty. The aim of the present case report is to indicate that fluorine-18-fluorodeoxy-glucose positron emission tomography/computerized tomography((18)F-FDG PET/CT) scan can be used for the evaluation of pain at the site of arthroplasty with a semi quantitative measurement. An 84 years old male patient, with a history of papillary thyroid cancer was referred to our Nuclear Medicine Department for an (18)F-FDG PET/CT scan for evaluation of his metastatic disease. He reported right hip prosthesis thirty years ago and now suffered from significant pain in the right hip joint which on a scale from 1 to 10 could be rated as grade 8. White blood cell count, sedimentation rate and C-reactive protein were within normal limits. Four years ago he also had severe pain on the right leg that could be rated as grade 8, and underwent an (18)F-FDG PET/CT scan that showed a maximum standardized uptake value (SUV(max)) of 9.8. A year later, at a follow up (18)F-FDG PET/CT scan and under a similar severe pain, SUV(max) was 10. The patient had a hip prosthesis in the left leg 3 years ago, for which he reported pain that could be rated as grade 3 and the SUV(max) was then 3.7. The degree of (18)F-FDG uptake is related to cellular metabolic rate and to the number of glucose transporters. In inflammation, the activated inflammatory cells demonstrate increased expression of glucose transporters and the affinity of glucose transporters for deoxyglucose is increased by various cytokines and growth factors. Furthermore, when the mononuclear cells and the granulocytes are activated by certain infectious humoral stimuli, they use large amounts of glucose by the hexose monophosphate shunt and the rate of oxygen uptake is intensely increased, during the so called "respiratory burst". In the present case, it was interesting to note that the degree of (18)F-FDG uptake at the sites of loosening hip arthroplasty was related to the severity of pain. Signs of infection or inflammation although not obvious in our case, could not be excluded because sensitivity, specificity and accuracy of PET for detecting infection associated with hip prostheses has been reported to be, 90%, 89.3% and 89.5%, respectively and sensitivity and specificity for detecting periprosthetic inflammation 100% and 45.5%,respectively. In another study using as a criterion for periprosthetic infection the increased (18)F-FDG activity at the bone-prosthesis interface of the femoral component, sensitivity, specificity, positive and negative predictive values for the (18)F-FDG PET study where 85%, 93%, 80% and 95%, respectively. Inflammation, often intense, may be present in aseptic loosening and characterized by increased periprosthetic (18)F-FDG uptake. In conclusion, in our case the degree of (18)F-FDG uptake in a loosening hip arthroplasty was related to the severity of pain although inflammation or infection could also play some role. Further studies are required to prove this suggestion.

Balloon kyphoplasty: scintigraphy as the ultimate decision maker?

Balloon kyphoplasty is still controversial as a treatment for vertebral compression fractures (VCFs) due to osteoporosis. Nevertheless, the authors conducted a prospective study in 60 patients about the effectiveness of scintigraphy, after the conventional roentgenographic examination, as an ultimate decision maker for the identification of the levels to be treated. Seventy-one levels were radiographically and scintigraphically positive, were seen as active, and thus treated. Thirty-seven levels were radiographically negative but positive scintigraphically, were considered as imminent fractures, and thus treated. Ten levels were positive radiographically, but negative scintigraphically, and were not treated as they were considered as healed. The Oswestry Disability Score (100% = worst possible condition) improved from 38.8% +/- 39.5% at baseline, to 2.38% +/- 3.99% on the first postoperative day (p < 0.001), to 2.00% +/- 3.40% at 1 month (p < 0.001) and to 1.93% +/- 3.33% at 6 months (p < 0.001). This preliminary study gives a hint that scintigraphy might work as the ultimate decision maker, even when plain radiographs are negative. Further studies will be needed to compare patients with VCFs positive radiographically and scintigraphically, and other patients with VCFs negative radiographically, but positive scintigraphically.

High (18)F-FDG uptake by the remaining adrenal gland four months after surgery and initiation of mitotane treatment in two patients with adrenocortical carcinoma.

Two men, one 42 and the other 35 years old were both subjected to adrenalectomy for adrenocortical carcinoma (ACC). Adjuvant treatment with mitotane [o,p΄-dichloro-diphenyl-dichloroethane, (o,p΄-DDD)], was initiated following surgery. Mitotane is the only agent available at present for treatment in ACC because of a late-onset specific adrenocortical cell toxicity. Both patients underwent a (18)F-FDG-PET/CT scan, which revealed 4 months after starting treatment with mitotane significantly high (18)F-FDG uptake in the contralateral adrenal gland. Both patients underwent magnetic resonance imaging, while one had a laparotomy, because of an abcess at the site of previous adrenalectomy. No metastasis or size increase of the remaining adrenal glands were found suggesting that their hypermetabolic state could be attributed to mitotane treatment. Beside its cytotoxic delayed-effect, mitotane has an early -onset effect on steroid metabolism. In conclusion, an abnormal high (18)F-FDG uptake was observed in the contralateral adrenal gland in both our adrenalectomized ACC patients, 4 months after starting mitotane treatment, probably related to mitotane's effect on steroid metabolism, not yet fully understood.

Routine needle biopsy during vertebral augmentation procedures. Is it necessary?

Vertebral augmentation procedures are currently widely performed to treat vertebral compression fractures. The purpose of this study was to determine the frequency of underlying previously unrecognized etiology in a consecutive series of patients undergoing kyphoplasty to treat vertebral compression fractures. A prospective histological evaluation of vertebral body biopsy specimens from presumed osteoporotic vertebral compression fractures were performed in order to identify aforementioned causes. Over a 2-year period, vertebral body biopsies from 154 vertebral levels were performed in 75 patients undergoing kyphoplasty for vertebral compression fractures. All patients received a preoperative workup that included plain radiographs, MRI, whole body bone scan, and laboratory examinations. Bone specimens were obtained from affected vertebral bodies and submitted for histologic evaluation to identify the prevalence of an underlying cause. All specimens demonstrated fragmented bone with variable amounts of unmineralised bone, signs of bone-remodeling and/or fracture-healing. In 11 patients underlying pathology other than osteoporosis was identified (prostate cancer, 1; pancreatic cancer, 1; colon cancer, 1; breast cancer, 2; multiple myeloma, 3; leukemia, 1; and lung cancer, 2). In all but one patient the results of the biopsy confirmed the diagnosis suspected from the preoperative workup. For the last patient, namely the one with pancreatic cancer, the workup did not identify the origin of the primary tumor, although the patient was considered to have a compression fracture secondary to metastatic disease of unknown origin, the vertebral biopsy suggested the presence of adenocarcinoma which eventually was proven to be pancreatic cancer. In augmentation procedures for vertebral compression fractures, bone biopsy should be reserved for the patients where the preoperative evaluation raises the suspicion of a non-osteoporotic etiology.

Low back pain: prediction of short-term outcome of facet joint injection with bone scintigraphy.

PURPOSE: To prospectively evaluate use of bone scintigraphy with single photon emission computed tomography (SPECT) for identification of patients with low back pain who would benefit from facet joint injections. MATERIALS AND METHODS: The protocol was reviewed and approved by the institutional review board. All patients provided informed consent. Forty-seven patients (23 men and 24 women) with low back pain, who were scheduled for facet joint injections, were prospectively enrolled and randomized into groups A and B (mean ages, 43.3 and 44.2 years, respectively) with a group A-group B ratio of 2:1. Group A patients underwent bone scintigraphy with SPECT prior to injection. Group A patients with bone scans positive for facet joint abnormalities received injections at the levels where abnormalities were identified on the scan (group A1). Group A patients with negative scans (group A2) received injections at the levels that were decided as in group B. Group B patients received injections at the levels indicated by the referring physician and did not undergo bone scintigraphy. All patients completed a pain and function questionnaire before injection and at 1, 3, and 6 months afterward. The change in the American Academy of Orthopaedic Surgeons pain scores after 1, 3, and 6 months compared with baseline scores was analyzed with analysis of variance and post hoc Bonferroni multiple-comparison tests between groups. Cost analysis was performed. RESULTS: The change in the pain score at 1 month was significantly higher (P < .004) in group A1 than it was in the other two groups. In group A1, 13 of 15 patients had improvement in pain score of greater than 1 standard deviation at 1 month, whereas improvement occurred in only two of 16 patients in group A2 and five of 16 patients in group B. In patients with positive scans, the number of facets treated with injection was decreased from 60, which was the number originally indicated by the referring physician, to 27. The Medicare cost was reduced from $2191 per patient to $1865 with the use of SPECT. CONCLUSION: Bone scintigraphy with SPECT can help identify patients with low back pain who would benefit from facet joint injections.

Superinfection of chronic multifocal osteomyelitis with Enterobacter cloacae.

A case is presented of a 6-year-old boy from Nigeria who developed chronic multifocal osteomyelitis with bilateral and symmetrical proximal humeral involvement. Superimposed changes of acute osteomyelitis were noted on the histopathological evaluation of the lesions. Cultures from both sides were positive for Enterobacter cloacae, which was presumably contracted during intravenous therapy for typhoid fever in Nigeria 1 month prior to his presentation.

The effects of rotation on radiographic evaluation of the tibiofibular syndesmosis.

Radiographs of 12 normal cadaveric lower extremities were prepared with each extremity in seven increments of axial rotation, ranging from 5 degrees of external rotation to 25 degrees of internal rotation. The tibiofibular clear space, the tibiofibular overlap, the width of the tibia and fibula, and the medial clear space were measured on each film. The width of the tibiofibular clear space (syndesmosis A) averaged 3.9+/-0.9 mm (range, 2 to 5.5 mm), but did not change significantly with rotation. Its size was independent of the size of tibia and fibula. All other measurements changed dramatically with rotation. In our specimens, a true mortise view of the ankle joint was obtained by internally rotating the extremity an average of 13.6+/-0.7 degrees (range, 12.0 degrees to 17.0 degrees). Based on our results the width of the tibiofibular clear space on the anterior-posterior view is the most reliable parameter for detecting widening of the syndesmosis on plain radiographs. However, due to its variability among different individuals, comparison views of the contralateral extremity are warranted for confirmation of clinical suspicion of syndesmosis disruption.