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Purpose. To present our results after short-term (1 month) intra-arterial infusion therapy of PGE1-alprostadil via a port system implanted in the ipsilateral external iliac artery (EIA) in patients with severe rest pain. Methods. Ten patients with severe rest pain were included. All patients showed extensive peripheral vascular disease below the knee. The tip of the catheter was introduced via a retrograde puncture in the ipsilateral external iliac artery (EIA). The patients received intraarterial infusion of PGE1, 20 mgr alprostadil daily, via the port catheter for 1 month. Results. Clinical success was evaluated according to subjective grading of pain (group A significant decrease, group B moderate decrease and group C no response). A significant decrease of rest pain was observed in 8 (group A, 80%) patients, a moderate decrease in 2 (Group B, 20%), whereas no patients demonstrated any significant response. Both patients of group B had Buergers' disease and continue to smoke during therapy. No peripheral thrombosis or clinical deterioration was noticed. Conclusion. Intraarterial infusion of PGE1 alprostadil on a daily basis, using a port catheter into the ipsilateral EIA, in selected patients with severe rest pain, seems to be very effective, without any serious complications.

The study aimed to assess the image quality and diagnostic performance of low-dose Chest Computed Tomography (LDCCT) in detecting pulmonary infections in patients with hematologic malignancies. A total of 164 neutropenic patients underwent 256 consecutive CT examinations, comparing 149 LDCCT and 107 Standard-Dose Chest CT (SDCCT) between May 2015 and June 2019. LDCCT demonstrated a 47% reduction in radiation dose while maintaining acceptable image noise and quality compared to SDCCT. However, LDCCT exhibited lower sensitivity in detecting consolidation (27.5%) and ground glass opacity (64.4%) compared to SDCCT (45.8% and 82.2%, respectively) with all the respective p -values from unadjusted and adjusted for sex, age, and BMI analyses being lower than 0.006 and the corresponding Odds Ratios of detection ranging from 0.30 to 0.34. Similar trends were observed for nodules ≥3 mm and ground glass halo in nodules but were not affected by sex, age and BMI. No significant differences were found for cavitation in nodules, diffuse interlobular septal thickening, pleural effusion, pericardial effusion, and lymphadenopathy. In conclusion, LDCCT achieved substantial dose reduction with satisfactory image quality but showed limitations in detecting specific radiologic findings associated with pulmonary infections in neutropenic patients compared to SDCCT.

Pancreatic ductal adenocarcinoma (PDAC) constitutes a leading cause of cancer-related mortality despite advances in detection and treatment methods. While computed tomography (CT) serves as the current gold standard for initial evaluation of PDAC, its prognostic value remains limited, as it relies on diagnostic stage parameters encompassing tumor size, lymph node involvement, and metastasis. Radiomics have recently shown promise in predicting postoperative survival of PDAC patients; however, they rely on manual pancreas and tumor delineation by clinicians. In this study, we collected a dataset of pre-operative CT scans from a cohort of 40 PDAC patients to evaluate a fully automated pipeline for survival prediction. Employing nnU-Net trained on an external dataset, we generated automated pancreas and tumor segmentations. Subsequently, we extracted 854 radiomic features from each segmentation, which we narrowed down to 29 via feature selection. We then combined these features with the Tumor, Node, Metastasis (TNM) system staging parameters, as well as the patient's age. We trained a random survival forest model to perform an overall survival prediction over time, as well as a random forest classifier for the binary classification of two-year survival, using repeated cross-validation for evaluation. Our results exhibited promise, with a mean C-index of 0.731 for survival modeling and a mean accuracy of 0.76 in two-year survival prediction, providing evidence of the feasibility and potential efficacy of a fully automated pipeline for PDAC prognostication. By eliminating the labor-intensive manual segmentation process, our streamlined pipeline demonstrates an efficient and accurate prognostication process, laying the foundation for future research endeavors.

Purpose: Accurate antenatal diagnosis of placenta accreta spectrum (PAS) is important for optimal management. The purpose of this study was to compare the respective capabilities of 1.5-T and 3.0-T MRI in the diagnosis of PAS., Materials and Methods: Between March 2016-March 2021, 190 pregnant women at high risk for PAS underwent dedicated prenatal MRI with either 1.5-T or 3.0-T units at a tertiary imaging center. Cesarian section and MRI were performed less than 6 weeks from each other. Prospectively collected data were evaluated by two experienced genitourinary radiologists for presence and extent of PAS. A comparative study was designed to investigate differences in predictive ability between 1.5-T and 3.0-T MRI groups. Sensitivity, specificity, accuracy, negative and positive prognostic values relative to intraoperative/histological findings, were computed for both groups and were compared with chi-square (χ 2) test. Interobserver agreement was estimated using Kappa test., Results: One hundred-eighty-two gravid women were included in the study; of these, 91/182 (50%) women were evaluated with 1.5-T (mean age, 35 ± 5.1 [SD] years; mean gestational age: 32.5 weeks) and 91/182 (50%) with 3.0-T MRI (mean age, 34.9 ± 4.9 [SD] years; mean gestational age, 32.1 weeks). 1.5-T MRI yielded 95.7% sensitivity (95% CI: 87.8-99.1) and 81.8% specificity (95% CI: 59.8) and 3.0-T MRI 93.8% sensitivity (95% CI: 86.0-97.9) and 83.3% specificity (95% CI: 48.2-97.7) for PAS identification, with no differences between the two groups (P = 0.725 and P >0.999, respectively). MRI showed excellent predictive ability for detecting extrauterine placental spread with 100% sensitivity (95% CI: 89.4-100.0), 96.7% specificity (95% CI: 88.1-99.6) for 1.5-T and 97% sensitivity (95% CI: 84.2-99.9), 96.7% specificity (95% CI: 88.1-99.6) for 3.0-T without differences between the two groups (P > 0.999). Interobserver agreement was excellent for both groups. The most frequently detected MRI signs of PAS for both 1.5-T and 3.0-T groups were placental heterogeneity (n = 85, 93.5% vs. n = 90, 98.9%; P = 0.413), and intraplacental fetal vessels (n = 64, 70.3% vs. n = 65, 71.4%; P = 0.870)., Conclusion: This study suggests that 3.0-T MRI and 1.5-T MRI are equivalent for the diagnosis of PAS., Competing Interests: Disclosure of interest The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper., (Copyright © 2022 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background An imaging-based predictor of response could provide prognostic information early during treatment course in patients with multiple myeloma (MM). Purpose To investigate if very early changes in bone marrow relative fat fraction (rFF) and apparent diffusion coefficient (ADC) histogram metrics, occurring after one cycle of induction therapy in participants with newly diagnosed MM, could help predict overall best response status. Materials and Methods This prospective study included participants with MM who were enrolled between August 2014 and December 2017. Histogram metrics were extracted from ADC and rFF maps from MRI examinations performed before treatment and after the first treatment cycle. Participants were categorized into the very good partial response (VGPR) or better group and the less than VGPR group per the International Myeloma Working Group response criteria. ADC and rFF map metrics for predicting treatment response were compared using the Wilcoxon rank test, and the false discovery rate (FDR) was used to correct for multiple comparisons. Results A total of 23 participants (mean age, 65 years ± 11 [SD]; 13 men) were evaluated. There was no evidence of a difference in ADC metrics between the two responder groups after correcting for multiple comparisons. The rFF histogram changes between pretreatment MRI and MRI after the first treatment cycle (ΔrFF) that provided significant differences between the VGPR or better and less than VGPR groups were as follows: ΔrFF_10th Percentile (median, 0.5 [95% CI: 0, 1] vs -2.5 [95% CI: -5.1, 0.1], respectively), ΔrFF_90th Percentile (median, 2 [95% CI: 1, 6.8] vs -0.5 [95% CI: -1, 0]), ΔrFF_Mean (median, 3.4 [95% CI: 0.3, 7.6] vs -1.1 [95% CI: -1.8, -0.7]), and ΔrFF_Root Mean Squared (median, 3.2 [95% CI: 0.3, 6.1] vs -0.7 [95% CI: -1.3, -0.4]) (FDR-adjusted P = .03 for all), and the latter two also presented mean group increases in the VGPR or better group that were above the upper 95% CI limit for repeatability. Conclusion Very early changes in bone marrow relative fat fraction histogram metrics, calculated from MRI examination at baseline and after only one cycle of induction therapy, may help to predict very good partial response or better in participants with newly diagnosed multiple myeloma. © RSNA, 2022 Online supplemental material is available for this article.

Contemporary information is sparse on the frequency of skeletal-related events (SREs) in multiple myeloma (MM) patients at a population-based level in the era of novel agents. In this context, we conducted this single-center, prospective, observational study to determine the incidence of SREs among newly diagnosed MMs (NDMM) and to explore the possible correlations with disease characteristics, imaging finding, and patient prognosis. A total of 370 patients with available baseline MRIs were included. Among them, 208 (56%) presented with at least one SRE at diagnosis. Fractures were the most common reported SREs (48%). The incidence of SREs at diagnosis was higher in patients with osteolytic lesions, abnormal MRI pattern, hypercalcemia, and at least 60% bone marrow infiltration by plasma cells. Importantly, the patients with normal MRI pattern, who did not present with SREs at diagnosis, had statistically significant improved median OS in comparison with the patients who had abnormal MRI patterns and/or the presence of SREs at diagnosis (9.3 vs. 6.6 years, p = 0.048). Our data, which represent one of a few systematic reports on the incidence and characteristics of SREs in the era of novel agents, was indicative of a high incidence of SREs at the time of MM diagnosis. Early detection of myeloma bone disease and tailored patient management are essential to optimize patient outcomes.

OBJECTIVE. The purpose of this article is to analyze whole-body low-dose CT-detected appendicular medullary patterns of attenuation in patients with newly diagnosed multiple myeloma and to determine the diagnostic performance of whole-body low-dose CT in detecting diffuse marrow infiltration. MATERIALS AND METHODS. A total of 76 patients with myeloma who underwent whole-body low-dose CT and spinal MRI at initial assessment were retrospectively analyzed. The medullary cavities of femurs and humeri were evaluated qualitatively and quantitatively on CT. Medullary attenuation and SD-to-mean attenuation ratio were recorded for each long bone. The pattern of marrow involvement on spinal MRI was used as reference. The chi-square test was used to evaluate the relationship between the CT-based appendicular medullary cavity pattern and the MRI pattern, and ROC analysis was performed to assess the diagnostic accuracy of CT attenuation measurements for the differentiation between diffuse and mixed CT-based appendicular medullary cavity patterns. RESULTS. Medullary attenuation differed significantly among mixed, nodular, and diffuse CT-based appendicular medullary cavity patterns in the femurs (mean, 34.23 HU and range, 15-61 HU; mean, 66.26 HU and range, 26-104 HU; mean, 92.80 HU and range, 53-127 HU, respectively) and humeri (mean, 22.18 HU and range, 9-41; mean, 61.18 HU and range, 23-93 HU; mean, 77.50 and range, 25-105 HU, respectively). To discriminate between diffuse and mixed CT-based appendicular medullary cavity patterns, optimal cutoff attenuation values were 63 HU (sensitivity, 97.7%; specificity, 100.0%) for the femurs, and 52 HU (sensitivity, 97.4%; specificity, 100.0%) for the humeri. A total of 24 of 30 (80.0%) patients with a diffuse MRI pattern showed a diffuse CT-based appendicular medullary cavity pattern on whole-body low-dose CT, and all patients with a diffuse CT-based appendicular medullary cavity pattern also showed a diffuse pattern on MRI. CONCLUSION. According to analysis of peripheral medullary patterns of attenuation, whole-body low-dose CT can identify patients with multiple myeloma with diffuse marrow involvement.

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by plasma cell bone marrow infiltration and end-organ involvement. Smoldering MM (SMM) is an intermediate clinical entity between MGUS and MM, with a risk of progression to symptomatic disease 10% per year. Bone disease is the most frequent symptom of MM, with ~90% of patients developing bone lesions throughout their disease course. Therefore, imaging plays a crucial role in diagnosis and management. Whole-body low-dose CT (WBLDCT) is widely available and has been incorporated in the latest diagnostic criteria of the IMWG. The purpose of this study was to evaluate the role of WBLDCT in the early identification of lesions in patients with SMM who progress solely with bone disease. In total, 100 asymptomatic patients were consecutively assessed with WBLDCT from July 2013 until March 2020 at baseline, 1-year after diagnosis and every 1 year thereafter. Ten percent of patients were identified as progressors with this single imaging modality. This is the first study to evaluate prospectively patients with SMM at different time points to identify early bone lesions related to MM evolution. Serial WBLDCT studies can identify early myeloma evolution and optimize disease monitoring and therapeutic strategies.

Aim: To retrospectively assess the effectiveness and safety of BLES stereotactic biopsy of suspicious calcifications and investigate possible predictive factors for underestimation., Methods and Materials: Between January 2014 and January 2016, 400 biopsies of suspicious calcifications were performed in our Department using the BLES stereotactic device. The mean age of our population was 58.5 years (range 39-78 years). The final surgical results were used as gold standard. The effectiveness of the method was statistically evaluated. Mammographic size, grade, molecular type, and presence of comedo type/necrosis were assessed as predictive factors., Results: 90/400 (22.5%) cases were cancers (20% invasive cancers, 80% non-invasive cancers). 38/400 cases were atypical lesions (9.5%). No underestimation was found in atypical lesions that underwent surgery (29/38 cases). Downgrade was achieved in 45.5% of cases (with complete removal in 34.4%), concordance in 43.3%, and upgrade was found in 15.5% of the cases; the initial mammographic size and the grade of the cancers were found to be statistically significant predictive factors. The total complication rate was 8.75%., Conclusions: Breast lesion excision system is a highly accurate and safe stereotactic biopsy technique of suspicious calcifications with low underestimations and high downgrade/removal rates with the potential to alter the final surgical decision in selected cases., (© 2019 Wiley Periodicals, Inc.)

Background: Frontotemporal dementia (FTD) represents the second most frequent early onset of dementia in people younger than 65 years. The main syndromes encompassed by the term FTD are behavioral variant of Frontotemporal dementia (bvFTD), non-fluent variant primary progressive aphasia (nfvPPA) and semantic variant (SD)., Aims: To assess the bvFTD and SD, which represent the most common subtypes of FTD, using visual rating scales., Methods: Brain MRI exams of 77 patients either with bvFTD (n=43) or SD (n=34) were evaluated. The rating scales used were: Global cortical atrophy (GCA), Fazekas Scale: periventricular (PV) and white matter (WM) changes, Koedam rating scale and visual scales regarding specific cortical regions: dorsofrontal (DF), orbitofrontal (OF), anterior cingulate (AC), basal ganglia (BG), anterior- temporal (AT), insula, lateral-temporal (LT), entorhinal (ERC), perirhinal (PRC), anterior fusiform( AF), anterior hippocampus (AHIP) and posterior hippocampus (PHIP). Both Left (L) and Right (R) hemispheres were evaluated., Results: R-OF (p=0.059), L-OF (p<0.0005), L-AT (p=0.047) and L-AHIP (p=0.007) have a statistically significant effect on the variable occurrence of SD compared to bvFTD. The indicators with the highest value of the area under the curve (AUC) were R-AC (0.829), L-OF (0.808), L-AC (0.791) and L-AF (0.778). Highest sensitivity was achieved by R-OF (97%) and L-AF (75%). Highest specificity was achieved by L-OF (95%), L-AT (91%) followed by R-AC (84%). Best combination of sensitivity and specificity was achieved by L-AF (74%-79%), L-OF (56%-95%) and R-OF (97%-42%). Best combination of PPV and NPV was achieved by L-OF (90%-73%), LAT (83%-72%) and R-AC (77%-77%)., Conclusion: Visual rating scales can be a practical diagnostic tool in the characterization of patterns of atrophy in FTLD and may be used as an alternative to highly technical methods of quantification., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To retrospectively assess the stereotactic one-pass BLES performance in excision of small groups of calcifications seen on mammogram that proved to be papillomas., Methods: Between January 2014 and January 2016, 37/400 cases (9.2%) of stereotactic BLES biopsies performed in our department due to suspicious calcifications proved to be papillomas. Lesions with atypia underwent surgical removal and lesions with no atypia were followed up for 2 years. BLES and surgical histology results, radiological removal and 2-years stability were statistically analysed to assess BLES performance in biopsy and excision of papillomas., Results: The mean mammographic size of papillomas was 6.54 mm (st dev = 3.85, range 2 mm-17 mm) and within the size excised by the BLES needle (20 mm). 4/37 cases (10.8%) showed atypia. BLES excision was achieved in 29/37 cases (78.4%); radiological removal based on post BLES mammogram was achieved in 25/29 cases (86.2%). In the remaining 8/37 cases the papillomas were seen at the ink of the specimens' margins; 3/8 cases showed residual calcifications on post-BLES mammogram. The BLES histology result of removal and the mammographic size of the papillomas were found to be statistically significant predictive factors of excision (p < 0,001, Fisher's exact test, Mann Whitney test). Follow up mammograms showed no change for a period of 2 years., Conclusion: BLES is a safe and accurate technique to biopsy papillomas with high success rates of excision which could potentially minimize the need of subsequent radiological or surgical excision., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Two fossilized human crania (Apidima 1 and Apidima 2) from Apidima Cave, southern Greece, were discovered in the late 1970s but have remained enigmatic owing to their incomplete nature, taphonomic distortion and lack of archaeological context and chronology. Here we virtually reconstruct both crania, provide detailed comparative descriptions and analyses, and date them using U-series radiometric methods. Apidima 2 dates to more than 170 thousand years ago and has a Neanderthal-like morphological pattern. By contrast, Apidima 1 dates to more than 210 thousand years ago and presents a mixture of modern human and primitive features. These results suggest that two late Middle Pleistocene human groups were present at this site-an early Homo sapiens population, followed by a Neanderthal population. Our findings support multiple dispersals of early modern humans out of Africa, and highlight the complex demographic processes that characterized Pleistocene human evolution and modern human presence in southeast Europe.

Purpose: To assess the role of the breast lesion excision system (BLES) in complete removal of clusters of microcalcifications found on mammogram proved histologically to be high-risk lesions with cell atypia., Methods and Materials: Three hundred ninety-four consecutive women (mean age 58.5 years, range 39-78 years) with 400 clusters of suspicious microcalcifications underwent stereotactic biopsy using the intact BLES device between January 2014 and January 2016. All cases proved histologically to be high-risk lesions were subsequently assessed for complete removal. The underestimation rate was also assessed., Results: Thirty-eight out of 400 (9.5%) lesions were high-risk lesions with atypia with mean size 7.63 mm (st. dev. = 4.03 mm) which was within the size that the BLES needle can excise (20 mm). Four (10.5%) papillomas with atypia, 14 (36.8%) cases with flat epithelial atypia (FEA), 10 (26.3%) cases with lobular intraepithelial neoplasia (LIN-LIN 1, LIN 2), 8 (21.2%) with atypical ductal hyperplasia (ADH) and 2 (5.3%) cases with mucocele-like lesions (MLL) with atypia were found. Twenty-nine out of 38 lesions had subsequent surgery. Complete excision was achieved in 23/29 lesions (79.3%). No underestimation was found. Two-year mammographic stability was found in all lesions. Non-parametric statistical analysis showed no other significant predictive factor for complete excision apart from the distance of the lesions from the specimen margins (p = 0.031 Mann-Whitney test)., Conclusion: One-pass BLES intact biopsy technique is a safe method of complete removal of high-risk atypical lesions with high accuracy rates for certain histologies and could be potentially used as an alternative excision method to diagnostic surgery in selected cases., Key Points: • Breast lesion excision system (BLES) is an image-guided biopsy technique that uses radiofrequency to remove an intact piece of tissue including the target breast neoplasm. • Breast lesion excision system (BLES) under stereotactic guidance is able to accurately biopsy high-risk breast lesions expressed mammographically as clusters of suspicious microcalcifications. • BLES under stereotactic guidance is an accurate technique for en bloc excision of selected cases of small clusters of suspicious microcalcifications proved to be high-risk lesions with histopathologically disease-free margins of excision.

Objectives: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the "gold standard" procedure for patients with ulcerative colitis (UC) requiring surgical intervention. A de-functioning ileostomy is usually performed, as a step for the IPAA procedure. The aim of this study is to present the methodology and results of the routine double assessment of IPAA integrity in asymptomatic patients prior to the ileostomy reversal and evaluate its necessity., Methods: This is a retrospective study of 61 UC patients, who underwent IPAA construction, in 2010-2016. A diverting ileostomy was created after IPAA construction, which was reversed at least 3 months later. A double assessment, with pouchogram and pouchoscopy, of IPAA integrity was performed, before stoma closure. Post-operative symptoms and signs of complications, imaging studies, and endoscopic findings were recorded during follow-up., Results: Prior to the ileostomy reversal, both pouchoscopy and pouchogram identified no patient with evidence of anastomotic leakage. During a mean follow-up of 3.67 years after ileostomy reversal, 11 patients developed complications but only one had signs of leakage, which presented as a pouch-vaginal fistula. The specificity of both the pouchogram and pouchoscopy reached 100% and the negative predictive value ranged between 98.4 and 100%., Conclusions: The specificity of pouchoscopy and pouchogram prior to ileostomy closure, in asymptomatic patients with IPAA for UC, is very high in recognizing an intact anastomosis, but their combination did not alter the diagnostic accuracy or had any effect in further management. At least, pouchogram could be selectively performed only in patients with high-risk clinical indicators., Key Points: • The double assessment of ileal pouch-anal anastomosis with pouchogram and pouchoscopy, prior to ileostomy closure, specifically in patients with ulcerative colitis has not been evaluated before. • The specificity of pouchoscopy and pouchogram prior to ileostomy closure, in asymptomatic patients with IPAA for UC, is very high in recognizing an intact anastomosis. • However, their combination did not alter the diagnostic accuracy or had any effect in further management, in asymptomatic patients.

Purpose: To investigate differences in clinical features, MRI findings and tumor biomarker characteristics in screen-detected (SCD) and non-screendetected (NSCD) cancers., Material and Methods: A total of 62 women (mean age, 48.4 years; range, 33-68 years) with biopsy confirmed breast cancer who underwent preoperative breast MRI were retrospectively evaluated by two expert radiologists. The women were divided into two groups according to the mode of cancer detection (Group A: screen- detected, Group B: non-screen/symptomatic cancer) and clinical, histopathological, MRI characteristics and biomarker features in each group were evaluated., Results: NSCD tumors had significantly greater size (3.5 cm vs. 2.1 cm) and Ki-67 expression (68.4% vs. 41.7%) in comparison to SCD cancers. NSCD cancers were less likely to have strongly positive progesterone receptors (Pr) and more likely to have Ki-67 > 15% or positive nodal status (47.4% vs. 8.3%). Increased breast density (ACR C and D: 78.9% vs. 50%ACR A and B) and intense background parenchymal enhancement (BPE, moderate/marked: 42.1% vs. 8.3% minimal/mild) were significantly more frequent in NSCD cases., Conclusion: NSCD cancers had higher prevalence of poor prognostic characteristics in comparison to SCD tumors, including larger tumor size, higher Ki-67 index, and positive nodes. Increased fibroglandular tissue and intense BPE were both strongly associated with NSCD cancers, supporting their use as potential MR biomarkers in breast cancer risk models., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders.

MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as diffusion-weighted imaging (spinal or whole body), intravoxel incoherent motion, and dynamic contrast enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma. These non-invasive functional techniques are also being evaluated as imaging biomarkers for response assessment in myeloma patients. The purpose of this article is to provide a comprehensive critical review on the current use and potential future applications of these advanced MRI techniques in multiple myeloma. In addition, we will address the technologies involved and describe the qualitative and quantitative characteristics of normal bone marrow with these techniques.

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99m Tc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe 3 O 4 -DMSA-SMCC-BCZM- 99m Tc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe 3 O 4 -DMSA-SMCC-BCZM- 99m Tc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe 3 O 4 -DMSA-SMCC-BCZM- 99m Tc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe 3 O 4 -DMSA-SMCC-BCZM- 99m Tc for targeted dual-modality imaging. Our findings indicate that Fe 3 O 4 -DMSA-SMCC-BCZM- 99m Tc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.

The aim of the study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with newly diagnosed multiple myeloma (MM) who were treated with novel anti-myeloma agents. We studied 60 previously untreated MM patients at diagnosis, 14 with smoldering MM (SMM) and 5 with MGUS. All patients underwent MRI of the thoracolumbar spine and pelvis before the administration of any kind of therapy, and DCE-MRI was performed. The MRI perfusion parameters evaluated were wash-in (WIN), washout (WOUT), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio. The following serum levels of angiogenic cytokines were measured on the day of MRI: VEGF, angiogenin (Ang), angiopoietin-1 (Angp-1), and -2 (Angp-2). Symptomatic MM patients had increased WIN compared to SMM (p < 0.05) and MGUS patients (p = 0.001). TTPK was decreased, and WIN/TMSP was increased in both symptomatic and SMM patients compared to MGUS patients (p < 0.05). Symptomatic MM patients had decreased TMSP compared to MGUS patients. The Angp-1/Angp-2 ratio was reduced in symptomatic MM compared to SMM (p = 0.017) and MGUS patients (p < 0.001). TTPK correlated with Angp-1/Angp-2 ratio and importantly with R-ISS. Patients with R-ISS-3 had lower TTPK median value (23 s, range 18-29 s) compared to patients with R-ISS-2 (48 s, range 27-68 s) and patients with R-ISS-1 MM (54 s, range 42-76 s; p ANOVA = 0.01). A subset of patients with low TTPK (lower quartile) had shorter time to progression compared to all other patients. These data suggest that certain DCE-MRI parameters correlate with R-ISS and adverse prognostic features of angiogenesis, such as the ratio of Angp-1/Angp-2.

Background and Aim: Fistula-in-ano is a common problem among patients with Crohn's disease and carries significant morbidity. We aimed to study the outcomes of surgical treatment of fistula-in-ano after fistulotomy or seton placement in patients with perianal fistulizing Crohn's disease., Material and Methods: A retrospective observational study of 59 patients diagnosed with Crohn's disease, who were treated surgically for fistula-in-ano between 2010 and 2014 in our department. The assessment of disease complexity included a detailed physical examination, magnetic resonance imaging of the rectum, and examination under anesthesia. Outcomes for analysis included wound healing rate and postoperative incontinence., Results: High transsphincteric fistula was found in 44% of the patients, while mid or low transsphincteric fistulas were found in 51%. Three women (5%) had a rectovaginal fistula. All patients with high transsphincteric fistulas were treated with loose seton placement. Patients with mid- or low-level transsphincteric fistula were offered either fistulotomy or seton placement based on the clinical evaluation. The mean follow-up duration was 1.6 ± 1.1 years. In terms of recurrence, one patient treated with seton placement presented with recurrence 6 months after seton removal and one patient with fistulotomy failed to achieve wound healing. Minor incontinence was found in six patients treated with fistulotomy and in three patients treated with seton placement; however, this difference was not significant (chi-square = 1.723, df = 1, Monte-Carlo: p = 0.273)., Conclusion: Fistulotomy could achieve good results in terms of wound healing and incontinence in strictly selected patients with Crohn's disease suffering from low-lying transsphincteric fistulae. For more high-lying or complicated fistulae, seton placement is more appropriate. For high transsphincteric fistulae, the only option is placement of loose seton.

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT. In comparison, WBCT failed to detect some bone destructions in the appendicular skeleton possibly due to limitations of the field of view. Presence of lytic bone lesions in WBCT was of borderline prognostic significance (P=0.051) for SMM patients, with a median time to progression of 38 versus 82 months for those without bone destructions. In conclusion, WBCT identifies significantly more sites of bone destruction than CSS. More than 20% of patients with SMM according to CSS have in fact active MM detectable with WBCT. On the basis of this and other studies, WBCT (either computed tomography (CT) alone or as part of a positron emission tomography-CT protocol) should be considered the current standard for the detection of osteolytic lesions in MM.

Aim: The aim of this study was to develop a dual-modality positron emission tomography/magnetic resonance (PET/MR) imaging probe by radiolabeling gadolinium-containing AGuIX derivatives with the positron-emitter Gallium-68 ( 68 Ga)., Materials & Methods: AGuIX@NODAGA nanoparticles were labeled with 68 Ga at high efficiency. Tumor accumulation in an appropriate disease model was assessed by ex vivo biodistribution and in vivo PET/MR imaging., Results:   68 Ga-AGuIX@NODAGA was proven to passively accumulate in U87MG human glioblastoma tumor xenografts. Metabolite assessment in serum, urine and tumor samples showed that 68 Ga-AGuIX@NODAGA remains unmetabolized up to at least 60 min postinjection., Conclusion: This study demonstrates that 68 Ga-AGuIX@NODAGA can be used as a dual-modality PET/MR imaging agent with passive accumulation in the diseased area, thus showing great potential for PET/MR image-guided radiation therapy.

Purpose To evaluate the apparent diffusion coefficients (ADCs) of magnetic resonance (MR) imaging patterns in the bone marrow of patients with multiple myeloma (MM) and to determine a threshold ADC that may help distinguish a diffuse from a normal pattern with high accuracy. Materials and Methods This prospective study was approved by the ethics review board, and informed consent was obtained. Ninety-nine patients with newly diagnosed, untreated MM and 16 healthy control subjects underwent spinal MR imaging including diffusion-weighted imaging, and bone marrow ADCs were calculated. Pattern assignment was based on visual assessment of conventional MR images. The Kruskal-Wallis H test, the Mann-Whitney test, and the one-way analysis of variance were used to compare ADCs between patient subsets and control subjects, and a receiver operating characteristic analysis was performed. Results Mean ADCs ± standard deviation in patients with MM for the normal, focal, and diffuse MR imaging patterns were 0.360 × 10 -3 mm 2 /sec ± 0.110, 1.046 × 10 -3 mm 2 /sec ± 0.232, and 0.770 × 10 -3 mm 2 /sec ± 0.135, respectively. There were significant differences in ADCs between diffuse and normal (P < .001), diffuse and focal (P < .001), and focal and normal (P < .001) patterns. Patients with a diffuse pattern had more features of advanced disease, higher international staging system score, increased incidence of high-risk cytogenetics, and higher revised international staging system score. ADCs greater than 0.548 × 10 -3 mm 2 /sec showed 100% sensitivity (26 of 26) and 98% specificity (48 of 49) for the diagnosis of a diffuse (vs normal) MR imaging pattern, whereas an ADC greater than 0.597 × 10 -3 mm 2 /sec showed 96% sensitivity (25 of 26) and 100% specificity (49 of 49). Conclusion ADCs of MR imaging patterns in patients with MM differ significantly. A diffuse MR imaging pattern can be distinguished more objectively from a normal MR imaging pattern by adding quantitative diffusion-weighted imaging to standard MR imaging protocols. © RSNA, 2016 Online supplemental material is available for this article.

Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate. All patients were found positive for NMO IgG. All patients (three with NMO and two with NMOSD, 1 patient with recurrent optic neuritis and 1 patient with recurrent myelitis) had received rituximab treatment for six years. One patient with NMOSD received cyclophosphamide prior to rituximab while two were misdiagnosed as multiple sclerosis and had received interferon treatment. All received rituximab infusion of 375mg/m 2 once per week for 4weeks and then every two months for the first two years and then every six months. B-cell counts were measured every two months and were kept in almost undetectable levels. No relapse was noted during the treatment period while EDSS score was improved in all patients. No severe adverse effects occurred during RTX treatment. Rituximab treatment on NMO and NMOSD patients showed significant improvement in disability and relapse-rate without any significant adverse effects., (Copyright © 2016. Published by Elsevier B.V.)

Purpose: Interruption of natalizumab (NTM) treatment in multiple sclerosis (MS) patients may be followed by disease reactivation. On the other hand, patients with positive John Cunningham virus (JCV) antibodies treated with NTM over 24 months demonstrate a higher risk for developing progressive multifocal encephalopathy (PML). No established therapeutic approach is available for treating these patients to prevent disease reactivation., Materials and Methods: Of the MS patients treated with NTM at the authors' institution, 30 were found positive for JCV abs. NTM was interrupted followed by a washout period of 6 months. During this period, 20/30 patients received monthly intravenous (i.v.) methylprednisolone (MPD) 1000 mg infusion and regular clinical assessment. On months 3 and 6, brain MRI was performed and 1000 mg MPD was administered for 5 days., Results: All patients were clinically and radiologically stable at the time of NTM break. No clinical relapse was observed during the six-month washout period for the MS patients under monthly MPD treatment, while one patient had a relapse and active lesions in the MRI on month 6. Of the other patients not receiving i.v. MPD regularly after NTM withdrawal, one showed several active lesions in brain MRI and the other had a severe relapse., Conclusions: Despite the limited size of this patients' cohort, the results of this study support that monthly MPD treatment for 6 months may result in a clinically stable disease status, thus ensuring safe transition to another second-line therapy such as fingolimod, following NTM withdrawal.

This is to evaluate the predictive ability of clinical examination and preoperative magnetic resonance imaging (MRI) for the staging of early cervical cancer. We prospectively evaluated 115 patients with cervical cancer, International Federation of Gynecologic and Obstetrics (FIGO) stage .05) increased significantly (AUC=0.84, P<.05). Our results support the official incorporation of MRI into FIGO classification system., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ovarian cancer is the second most common gynecologic malignancy and is one of the leading causes of death among women. The disease course and the accurate diagnosis are correlated with the early detection of the lesion. About 5% of ovarian cancers are poorly differentiated and difficult to be classified, and are referred to as undifferentiated carcinomas. They are usually large, solid with haemorrhage and necrosis, bilateral, and very difficult to be histologically classified. Generally, cases with undifferentiated components are very rare. The authors present a case of a young female patient with a rapidly progressive undifferentiated ovarian carcinoma and a final unfortunate clinical result.

Endometriosis represents a main cause of infertility and pelvic pain affecting 3-43% among reproductive age women. Deep pelvic endometriosis is defined as subperitoneal infiltration of endometrial implants in the uterosacral ligaments, rectum, rectovaginal septum, vagina or bladder. The authors present a case of a 29-year-old patient who underwent laparoscopic excision of extensive endometriotic plaque in rectovaginal septum accompanied with deeply infiltrating endometriosis (DIE) and chronic pelvic pain (CPP).

Introduction: Vertebral hemangiomas are benign vascular tumours of the bony spine which are usually asymptomatic. Pregnancy-related anatomical and hormonal changes may lead to expansion of hemangiomas and development of neurological symptoms. We present an unusual case of vertebral fracture due to an undiagnosed hemangioma presenting as postpartum back pain following epidural analgesia., Case Presentation: A multiparous female with an unremarkable history developed intense lumbar pain after vaginal delivery under epidural analgesia. The pain was attributed to tissue trauma associated with the epidural technique. The patient had no clinical improvement with analgesics, and her symptoms deteriorated over the following days. A magnetic resonance imaging scan revealed an acute fracture of the second lumbar vertebra (L2) with epidural extension and mild compression of the dural sac, suggesting hemangioma as the underlying cause. The patient underwent successful spinal surgery with pedicle screw fixation to stabilize the fracture., Conclusion: Vertebral fractures secondary to acute expansion of a vertebral hemangioma rarely occur during vaginal delivery. In such cases, the labour epidural technique and analgesia may challenge the physician in making the diagnosis. Postpartum severe back pain should be thoroughly investigated even in the absence of neurological deficits, and osseous spinal pathology should be considered in the differential diagnosis.

Nanoparticles made of a polysiloxane matrix and surrounded by 1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid (DOTAGA)[Gd(3+) ] and 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) NODAGA[(68) Ga(3+) ] have been synthesized for positron emission tomography/magnetic resonance (PET/MRI) dual imaging. Characterizations were carried out in order to determine the nature of the ligands available for radiolabelling and to quantify them. High radiolabelling purity (>95%) after (68) Ga labelling was obtained. The MR and PET images demonstrate the possibility of using the nanoparticles for a combined PET/MR imaging scanner. The images show fast renal elimination of the nanoparticles after intravenous injection., (Copyright © 2014 John Wiley & Sons, Ltd.)