A measuring technique for intra-osseous pressure.

OBJECTIVE: Pulsatile intra-osseous pressures result in bone remodeling, and therefore may affect lesion growth and response to treatment. However, there is no known method used to measure intra-osseous pressures. The purpose of this study is to describe a novel image-guided technique for measuring intra-osseous pressures. MATERIALS AND METHODS: This study was IRB-approved and HIPAA compliant. Written informed consent was obtained. Intra-osseous pressure measurements were performed during a CT-guided bone marrow biopsy in eight patients (6 male, 2 female) with mean age 66 ± 13 years (median 72, range 45-87) and suspected or known bone marrow disease. Bone marrow pressure measurements were obtained connecting the biopsy needle to a dedicated monitor using a standard arterial line setup. Monitor data was collected at 5-s intervals in order to record continuous pressure measurements for 2 min. RESULTS: Pressure measurements were successfully performed in all 8 patients. The mean bone marrow pressures were 36.8 ± 7.2 mmHg (median 37.7, range 24.7-47.4). The peak and trough pressures varied by 11%, and the standard deviation of mean pressure measurement varied by 18%. Our findings for marrow pressure measures most closely approximate the pressure profile of the venous system. CONCLUSION: We describe a novel and minimally invasive technique able to provide functional data of bone marrow. This technique has the potential to provide insights into normal and diseased bone marrow and may be helpful to evaluate features of cystic and vascular tumors that may be amenable to percutaneous treatments.

Clinical, radiological, and pathological features of extraskeletal osteosarcoma.

OBJECTIVE: To evaluate clinical and radiological features of pathology-proven extraskeletal osteosarcomas. METHODS: This retrospective study was IRB-approved and HIPAA-compliant. Our pathology database was queried for cases of extraskeletal osteosarcoma. Tumor location, size, imaging appearance, presence of metastases, and clinical outcome were documented. RESULTS: Nineteen patients met inclusion criteria (age 59 ± 15 (range 28-85) years; 15 male, 4 female). Tumors occurred in the lower extremities (12 out of 19, 63%), pelvis/gluteal region (3 out of 19, 16%), upper extremity (2 out of 19, 5%), thorax (1 out of 19, 5%), and neck (1 out of 19, 5%). Two out of 19 (11%) patients had undergone radiation to the tumor site previously. According to pathology, 16 out of 19 tumors were high-grade (84%). Tumors presented as soft-tissue masses measuring 9.5 ± 6.8 (2-29) cm. Tumor mineralization was present in 5 out of 19 cases (26%) and local invasion was found in 1 out of 19 cases (6%). On MRI, tumors typically appeared hyperintense on T2-weighted sequences with enhancement in 15 out of 15 (100%) contrast-enhanced studies, and with central necrosis in 10 out of 19 (53%) cases. Low-grade tumors were smaller (<4 cm; 3 out of 3, 100%) and lacked central necrosis (3 out of 3, 100%). 8 out of 19 patients (42%) had metastases, most commonly to the lung (7 out of 19, 37%) and bone (2 out of 19,11%). Two out of 8 patients (25%) with metastases and 8 out of 11 (73%) without metastases achieved recurrence-free survival (mean follow-up 3.8 ± 4.0 [0.2-14.2]) years. No metastases or deaths occurred in patients with low-grade histology. CONCLUSIONS: Extraskeletal osteosarcomas are rare, typically high-grade malignancies that commonly metastasize to lung and bones. Low-grade tumors and those without metastases have a good prognosis. MRI appearance is nonspecific, with T2 hyperintense signal and heterogeneous enhancement. Unlike conventional osteosarcoma, mineralization is rare.

Demographic confounders in volumetric MRI analysis: is the posterior fossa really small in the adult Chiari 1 malformation?

OBJECTIVE: Measurement of posterior fossa volume has been proposed to have diagnostic utility and physiologic significance in the Chiari malformation type 1. This study evaluated the effects of demographics on posterior fossa volume and total intracranial volume in adult control subjects, adult patients with Chiari malformation type 1, and adult patients with idiopathic intracranial hypertension, who may share some imaging features of patients with Chiari malformation type 1. MATERIALS AND METHODS: Twenty-eight patients with Chiari malformation type 1, 21 patients with idiopathic intracranial hypertension, and 113 control subjects underwent brain MRI including contrast-enhanced 3D gradient-recalled echo (GRE) T1-weighted imaging. Linear measurements of the posterior fossa and intracranial space were obtained. Manual segmentation of the posterior fossa and intracranial space was performed to yield posterior fossa volume and total intracranial volume. Age, sex, race, and body mass index (weight in kilograms divided by the square of height in meters; BMI) were controlled for when comparing cohorts. RESULTS: Three of the 12 linear measurements significantly predicted total intracranial volume (accounting for 74% of variance), and four predicted posterior fossa volume (54% of variance). Age, race, sex, and BMI each statistically significantly influenced posterior fossa volume and total intracranial volume. No statistically significant differences in posterior fossa volume, total intracranial volume, or ratio of posterior fossa volume to total intracranial volume were seen between the Chiari malformation type 1 group and control group after controlling for demographics. Patients with idiopathic intracranial hypertension were more likely than control subjects to have smaller posterior fossa volumes (odds ratio [OR]=1.81; p=0.01) and larger total intracranial volumes (OR=1.24; p=0.06). CONCLUSION: Linear measurements of the posterior fossa are not strong predictors of posterior fossa volume. Age, race, sex, and BMI have statistically significant effects on intracranial measurements that must be considered, particularly with respect to posterior fossa volume in Chiari malformation type 1. Even when these demographic variables are appropriately accounted for, other similarly presenting diseases may show small posterior fossa volumes.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

OBJECTIVE: Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. MATERIALS AND METHODS: Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. RESULTS: Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). CONCLUSION: Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.

MRI, clinical, and radiomic models for differentiation of uterine leiomyosarcoma and leiomyoma.

PURPOSE: To assess the predictive ability of conventional MRI features and MRI texture features in differentiating uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS). METHODS: This single-center, IRB-approved, HIPAA-compliant retrospective study included 108 patients (69 LM, 39 LMS) who had pathology, preoperative MRI, and clinical data available at our tertiary academic institution. Two radiologists independently evaluated 14 features on preoperative MRI. Texture features based on 3D segmentation were extracted from T2W-weighted MRI (T2WI) using commercially available texture software (TexRAD™, Feedback Medical Ltd., Great Britain). MRI conventional features, and clinical and MRI texture features were compared between LM and LMS groups. Dataset was randomly divided into training (86 cases) and testing (22 cases) cohorts (8:2 ratio); training cohort was further subdivided into training and validation sets using ten-fold cross-validation. Optimal radiomics model was selected out of 90 different machine learning pipelines and five models containing different combinations of MRI, clinical, and radiomics variables. RESULTS: 12/14 MRI conventional features and 2/2 clinical features were significantly different between LM and LMS groups. MRI conventional features had moderate to excellent inter-reader agreement for all but two features. Models combining MRI conventional and clinical features (AUC 0.956) and MRI conventional, clinical, and radiomics features (AUC 0.989) had better performance compared to models containing MRI conventional features alone (AUC 0.846 and 0.890) or radiomics features alone (0.929). CONCLUSION: While multiple MRI and clinical features differed between LM and LMS groups, the model combining MRI, clinical, and radiomic features had the best predictive ability but was only marginally better than a model utilizing conventional MRI and clinical data alone.

Performance of VI-RADS in predicting muscle-invasive bladder cancer after transurethral resection: a single center retrospective analysis.

PURPOSE: To assess VIRADS performance and inter-reader agreement for detecting muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumor (TURBT). METHODS: An IRB-approved, HIPAA-compliant, retrospective study from 2016 to 2020 included patients with bladder urothelial carcinoma who underwent MRI after TURBT, and cystectomy within 3 months without post-MRI treatments. Three radiologists blinded to pathology results independently reviewed MR images and assigned a VI-RADS score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI-RADS were assessed for diagnosing MIBC using VI-RADS scores ≥ 3 and ≥ 4. Inter-reader agreement was assessed using Gwet's agreement coefficient (AC) and percent agreement. RESULTS: The cohort consisted of 70 patients (mean age, 68 years ± 11 [SD]; range 39-85; 58 men) and included 32/70 (46%) with MIBC at cystectomy. ROC analysis revealed an AUC ranging from 0.67 to 0.77 and no pairwise statistical difference between readers (p-values, 0.06, 0.08, 0.97). Percent sensitivity, specificity, PPV, NPV and accuracy for diagnosing MIBC for the three readers ranged from 81.3-93.8, 36.8-55.3, 55.6-60.5, 77.3-87.5, and 62.9-67.1 respectively for VI-RADS score ≥ 3, and 78.1-81.3, 47.4-68.4, 55.6-67.6, 72.0-78.8 and 61.4-72.9 respectively for VI-RADS score ≥ 4. Gwet's AC was 0.63 [95% confidence interval (CI): 0.49,0.78] for VI-RADS score ≥ 3 with 79% agreement [95% CI 72,87] and 0.54 [95%CI 0.38,0.70] for VI-RADS score ≥ 4 with 76% agreement [95% CI 69,84]. VIRADS performance was not statistically different among 31/70 (44%) patients who received treatments prior to MRI (p ≥ 0.16). CONCLUSION: VI-RADS had moderate sensitivity and accuracy but low specificity for detection of MIBC following TURBT, with moderate inter-reader agreement.

Interreader Agreement and Intermodality Concordance of O-RADS US and MRI for Assessing Large, Complex Ovarian-Adnexal Cysts.

Purpose To assess interreader agreement of the Ovarian-Adnexal Reporting and Data System (O-RADS) and intermodality concordance between US and MRI for characterizing complex adnexal cysts measuring 5 cm or larger. Materials and Methods This retrospective study included 58 "complex cysts" measuring at least 5 cm in size observed at both US and MRI in 54 women (median age, 37 years ± 12 [SD]; seven postmenopausal women) between July 2017 and June 2020, identified from an electronic US database. A separate set of two blinded radiologists independently reviewed the US or MR images to assign the O-RADS category, and an adjudicator resolved discrepancies (a total of six readers). Lesion outcome (49 benign, eight malignant, one lost to follow-up) was recorded. Interreader agreement of O-RADS US and O-RADS MRI and concordance between US and MRI were analyzed. Results Interreader agreement was fair for US (κ = 0.31), moderate for MRI (κ = 0.43), and moderate between US and MRI (κ = 0.58). A significant positive correlation was found between O-RADS US and MRI (τ = 0.72, P < .001). The O-RADS 4 threshold yielded the highest accuracy for both US and MRI (area under the receiver operating characteristic curve = 0.92 and 0.995, respectively). Considering O-RADS US 4 or 5 as potentially malignant and 1-3 as benign, eight lesions that were assessed as potentially malignant at US were correctly downgraded to benign by using findings at MRI. Using findings at MRI, one malignant lesion that was assessed as benign at US was upgraded to potentially malignant. Conclusion O-RADS US and MRI had excellent performance and positive correlation, but significant interobserver variability remains. Keywords: Ovary, MR Imaging, Ultrasonography © RSNA, 2022 See also the commentary by Baumgarten in this issue.

Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma.

The mutant IDH1 inhibitor ivosidenib improves outcomes for patients with IDH1-mutated cholangiocarcinoma, but resistance inevitably develops. Mechanisms of resistance and strategies to overcome resistance are poorly understood. Here we describe two patients with IDH1 R132C-mutated metastatic cholangiocarcinoma who developed acquired resistance to ivosidenib. After disease progression, one patient developed an oncogenic IDH2 mutation, and the second patient acquired a secondary IDH1 D279N mutation. To characterize the putative IDH1 resistance mutation, cells expressing the double-mutant were generated. In vitro, IDH1 R132H/D279N produces (R)-2HG less efficiently than IDH1 R132H. However, its binding to ivosidenib is impaired and it retains the ability to produce (R)-2HG and promote cellular transformation in the presence of ivosidenib. The irreversible mutant IDH1 inhibitor LY3410738 binds and blocks (R)-2HG production and cellular transformation by IDH1 R132H/D279N. These resistance mechanisms suggest that IDH1-mutated cholangiocarcinomas remain dependent on (R)-2HG even after prolonged ivosidenib treatment. Sequential mutant IDH inhibitor therapy should be explored as a strategy to overcome acquired resistance to mutant IDH inhibitors.