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Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Background: Post-contrast synovial thickness measurement is necessary for scoring disease activity in juvenile idiopathic arthritis (JIA). However, the timing of post-contrast sequences varies widely among institutions. This variation in timing could influence thickness measurements. Objective: To measure thickness of the synovial membrane on early and late post-contrast knee magnetic resonance (MR) images of patients with JIA. Materials and methods: Dynamic contrast-enhanced T1-weighted knee MR images of 53 children with JIA with current or past knee arthritis were used to study synovial thickness at time point 1 (about 1 min) and time point 2 (about 5 min after contrast administration). Two experienced readers, who were blinded for the time point, independently measured synovial thickness at a predefined, marked location in the patellofemoral compartment on randomized images. Synovial thickness at the two time points was compared using the Wilcoxon signed rank test. Repeatibility of the synovial thickness measurements was studied using intraclass correlation coefficients and Bland-Altman plots. Results: Median synovial thickness of the 53 patients (median age: 13.5 years, 59% female) increased with prolonged post-contrast interval with a synovial thickness of 1.4 mm at time point 1 and a synovial thickness of 1.5 mm at time point 2 (P

Purpose In this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM). Materials and methods In 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2 ml/kg body weight) was injected intravenously at a speed of 3 ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model. Results Sagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient–echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5 s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5 mm and two acquisitions. Conclusion The proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

The mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.

Background Dynamic contrast-enhanced MRI provides information on the heterogeneity of the synovium, the primary target of disease in children with juvenile idiopathic arthritis (JIA). Objective To evaluate the feasibility of dynamic contrast-enhanced MRI in the wrist of children with JIA using conventional descriptive measures and time-intensity-curve shape analysis. To explore the association between enhancement characteristics and clinical disease status. Materials and methods Thirty-two children with JIA and wrist involvement underwent dynamic contrast-enhanced MRI with movement-registration and were classified using validated criteria as clinically active (n = 27) or inactive (n = 5). Outcome measures included descriptive parameters and the classification into time-intensity-curve shapes, which represent the patterns of signal intensity change over time. Differences in dynamic contrast-enhanced MRI outcome measures between clinically active and clinically inactive disease were analyzed and correlation with the Juvenile Arthritis Disease Activity Score was determined. Results Comprehensive evaluation of disease status was technically feasible and the quality of the dynamic dataset was improved by movement registration. The conventional descriptive measure maximum enhancement differed significantly between clinically active and inactive disease (P = 0.019), whereas time-intensity-curve shape analysis showed no differences. Juvenile Arthritis Disease Activity Score correlated moderately with enhancing volume (P = 0.484). Conclusion Dynamic contrast-enhanced MRI is a promising biomarker for evaluating disease status in children with JIA and wrist involvement. Conventional descriptive dynamic contrast-enhanced MRI measures are better associated with clinically active disease than time-intensity-curve shape analysis. Electronic supplementary material The online version of this article (doi:10.1007/s00247-016-3736-2) contains supplementary material, which is available to authorized users.

OBJECTIVES: To assess the capability of the pixel-by-pixel DCE-MRI time intensity curve (TIC)-shape analysis method in the evaluation of juvenile idiopathic arthritis (JIA) disease activity by correlating DCE-MRI parameters with semi-quantitative conventional-MRI scores of synovitis.METHODS: Clinical, laboratory, and (DCE)-MRI datasets of 85 JIA patients were prospectively obtained. TIC-shapes of each voxel were classified into one of seven predefined color-coded TIC shape categories. Spatial information on the relative amount of TIC-shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV) was calculated of the synovial membrane. The grade of synovitis was scored on conventional MR images by two readers using the validated JAMRIS system. The Bonferroni method was used to correct for multiple testing, therefore, a P value of RESULTS: The semi-quantitative JAMRIS synovitis score correlated substantially with the ME, EV, and iAUC (Rs=0.658, PCONCLUSION: In this explorative study, both TIC shape and semi-quantitative DCE-MRI analysis methods showed moderate to substantial correlations with conventional MRI scores of disease activity, indicating that this methods are feasible. Further research is warranted whether DCE-MRI holds potential to become an objective and quantitative method for the evaluation of disease activity in JIA.

PURPOSE: The study was performed to determine whether conventional and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters of a previously affected target joint in patients with clinically inactive juvenile idiopathic arthritis (JIA) have prognostic meaning for a flare of joint inflammation during follow-up.MATERIAL AND METHODS: Thirty-two JIA patients with clinically inactive disease at the time of MRI of the knee were prospectively included. DCE-MRI provided both descriptive measures and time-intensity-curve shapes, representing functional properties of the synovium. Conventional MRI outcome measures included validated scores for synovial hypertrophy, bone marrow edema, cartilage lesions and bone erosions. During a 2-year period the patients were monitored by their pediatric rheumatologist and clinical flares were registered.RESULTS: MRI analysis revealed synovial hypertrophy in 13 (39.4%) of the clinically inactive patients. Twelve patients (37.5%) had at least one flare during 2-year clinical follow-up. Persistently inactive and flaring patients differed significantly in the maximum enhancement of the synovium on the DCE-MRI (pCONCLUSIONS: Our prospective clinical follow-up study indicates that the assessment of 'maximum enhancement' upon DCE-MRI may be able to predict a clinical flare within 2 years in inactive JIA patients.

Objectives: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Methods: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99m Tc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. Results: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863–0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. Conclusions: Assessment of liver function with DHCE-MRI is comparable with that of 99m Tc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. Key Points: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

PurposePharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration.MethodsWe propose an improved pharmacokinetic model for the liver that (1) analytically models the arrival-time of the contrast agent for both inputs separately; (2) implicitly compensates for signal fluctuations that can be modeled by varying applied flip-angle e.g. due to B1-inhomogeneity. Orton's AIF model is used to analytically represent the vascular input functions. The inputs are independently embedded into the Sourbron model. B1-inhomogeneity-driven variations of flip-angles are accounted for to justify the voxel's displacement with respect to a pre-contrast image.ResultsThe new model was shown to yield lower root mean square error (RMSE) after fitting the model to all but a minority of voxels compared to Sourbron's approach. Furthermore, it outperformed this existing model in the majority of voxels according to three model-selection criteria.ConclusionOur work primarily targeted to improve pharmacokinetic modeling for DCE-MRI of the liver. However, other types of pharmacokinetic models may also benefit from our approaches, since the techniques are generally applicable.

Objectives To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Methods Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. Results A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p

OBJECTIVE: To evaluate the feasibility of non-invasive diffusion-weighted imaging (DWI) of the knee of children with juvenile idiopathic arthritis (JIA) and, further, to analyze the apparent diffusion coefficient (ADC) levels to distinguish synovium from effusion.MATERIALS AND METHODS: Standard magnetic resonance imaging of the knee including post-contrast imaging was obtained in eight patients (mean age, 12 years 8 months, five females) using an open-bore magnetic resonance imaging system (1.0 T). In addition, axially acquired echo-planar DWI datasets (b-values 0, 50, and 600) were prospectively obtained and the diffusion images were post-processed into ADC50-600 maps. Two independent observers selected a region of interest (ROI) for both synovium and effusion using aligned post-contrast images as landmarks. Mann-Whitney U test was performed to compare ADC synovium and ADC effusion.RESULTS: DWI was successfully obtained in all patients. When data of both observers was combined, ADC synovium was lower than ADC effusion in the ROI in seven out of eight patients (median, 1.92 × 10(-3) mm(2)/s vs. 2.40 × 10(-3) mm(2)/s, p = 0.006, respectively). Similar results were obtained when the two observers were analyzed separately (observer 1: p = 0.006, observer 2: p = 0.04).CONCLUSIONS: In this pilot study, on a patient-friendly 1.0-T open-bore MRI, we demonstrated that DWI may potentially be a feasible non-invasive imaging technique in children with JIA. We could differentiate synovium from effusion in seven out of eight patients based on the ADC of synovium and effusion. However, to select synovium and effusion on DWI, post-contrast images were still a necessity.

The aim of the study was to evaluate the relationship between bacterial vaginosis (BV) and relapse of cervical intraepithelial neoplasia grade 2 or more (CIN2+) after Loop electrosurgical excision procedure (LEEP).One hundred four patients who underwent LEEP for CIN2+ were followed up every six months for three years. Fifty-three were negative for BV and fifty-one were positive. Each clinical control included Pap test, colposcopy, Amsel criteria test, HPV-DNA, and HPV-mRNA test.Patients' age, presence of BV, positivity to HPV-DNA and HPV-mRNA tests were analyzed. The average age of patients was 42.5 ± 8.92 years (median: 42.5; range from 27 to 58 years). The minimum follow-up was 6 months and maximum 36 months (average: 22.8 ± 4.53; median: 24). The 10% of the patients with HPV-mRNA test negative had relapsed, compared to 45% of patients with HPV-mRNA test positive. Among the 53 patients without BV the 20% had relapsed compared with 23% of 51 patients with diagnosis of BV.There is no evidence for higher percentage of relapse in patients with BV, submitted to excisional procedure for CIN2+ associated to HPV-m-RNA test positivity. There is only a correlation among BV and relapse of CIN2+ lesions after LEEP.

Infection of total knee arthroplasty (TKA) is a challenge in orthopedic surgery. In literature TKA infection is classified according to the time after surgery: acute postoperative; late chronic; acute hematogenous; positive intraoperative microbiological growth. The purpose of this study is to present the results of the use of a preformed antibiotic-loaded spacer in TKA infections, treated by a two-stage revision procedure. A series of 19 consecutive patients (20 knees) with a diagnosis of infected TKA were treated from January 2003 to February 2012. Two-stage reimplantation protocols were completed only in 16 patients and these data were included in the study. We lost three patients at follow-up. An antibiotic-loaded preformed articulating polymethylmethacrylate spacer was applied. Patients were observed 1, 3, and 6 months postoperatively and then yearly for clinical and radiographic examination. The mean American Knee Society Score improved from 68.4 preoperatively (range, from 34 to 108) to 112.7 at final follow-up (range, from 49 to 180). The pain was evaluated as part of clinical score. It improved from an average of 19.3 preoperatively (range, from 10 to 30) to 34.3 at final follow-up (range, from 10 to 50). The average range of motion improved from 40.1 degrees (range, from 6 to 90 degrees) to 79.3 degrees (range, from 45 to 125 degrees). The use of the spacer allows obtaining a reduction of pain, an improvement of quality of life in the period of time between the two surgical stages and an easier reimplantation of TKA.

The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract-based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H-MRS) in the left centrum semiovale (white matter) showed a reduction of N-acetylasparate/creatine indicative of axonal injury. Voxel-based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H-MRS only in the chemotherapy group. These results converge to suggest that high-dose adjuvant chemotherapy for breast cancer is associated with long-term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment. Hum Brain Mapp 33:2971-2983, 2012. (C) 2011 Wiley Periodicals, Inc

A clinical series of 17 adult patients operated due to significant by bone loss of the long bones of the lower extremity (3 femurs and 11 tibias), is presented. Their management consisted of 6 bone transports (6 tibias) and 11 compression distraction procedures (3 femurs and 8 tibiae) using monolateral external fixators. Bone loss ranged from 3.9 cm to 14.7 cm. Mean healing time was 301 days with a mean healing index of 45.6 days for cm of lengthening achieved. The clinical and radiological results were excellent in 9, good in 6 and fair in 2 patients according to the utilised criteria of assessment. Consolidation was achieved in all but one patient who developed an aseptic stiff non-union. Two patients developed residual limb-length discrepancy less than 1.5 cm, three tibias ended up with less than 5° of valgus deviation. In two cases the half-pins were re-inserted due to early loosening. In two cases reoperation was needed for late bending of the callus after fixator removal. Three cases of bone transport and 1 case of compression distraction needed bone grafting at the docking site. Bone transport and compression-distraction are effective methods for treating bone loss in the lower extremity. It is suggested that the compression-distraction technique is preferable, since this is associated with a lower incidence of complications than bone transport procedures. The deciding factor, however, is the actual extent of the bone loss.

We studied 80 patients (56 females) with an average age of 84 years (range 80-94). All patients were suffering from osteoporosis (1 or 2 Singh score) and had an unstable intertrochanteric fracture, defined as a fracture with three fragments or more. Patients were divided in group A (40 patients), treated by a cement augmentation technique and group B (40 patients) treated by Gamma Nail conventional technique. Augmentation was performed with MetilMetacrilate (Mendec Spine, Tecres) inserted through the cannulated cephalic screw at its apex. Such parameters were evaluated as the length of operating time, early functional recovery using the Harris hip score, assessment with radiography of the TAD index and development of implant related complications. The HHS average score was 48.2 and 49.31 after 1 month post-operation, 54.37 and 53.56 after 3 months, 54.71 and 56.42 after 6 months, 57.91 and 59.86 after 12 months, in groups A and B, respectively. The average drop of haemoglobin was 1.55 g/dL and 1.05 g/dL, in groups A and B, respectively. Except one joint penetration with the guide wire and some small amount of cement leakage, no other complications (infection, screw cut out and femoral head necrosis) were observed. We believe that in femoral intertrochanteric fractures cement augmentation could improve the mechanical stability of the implant, ensuring early functional recovery.

The aim of endovascular therapy in renal artery stenosis (RAS) is to preserve renal function and have a better hypertension control. The purpose of our study was to determine which biochemical and instrumental parameters could predict a better renal outcome in patients with RAS treated with percutaneous transluminal angioplasty and stenting (RPTAS).We performed an observational study based on 40 patients with RAS who met the following criteria before revascularization: urinary protein excretion of over 250 mg/24 h, normal renal function, and/or mild-moderate renal insufficiency (I, II, and III levels of classification of chronic kidney disease, K-DOQI).Assessment at 12 months after RPTAS showed in 20 patients (Group A) that proteinuria serum creatinine (Scr) and creatinine clearance (CrCl) significantly worsened from the baseline; whereas in 20 patients (Group B) proteinuria remained unchanged and the renal function improved after the procedure.In our study, the decline of renal function after RPTAS is associated with an elevated renal resistance index (RI) in both kidneys (0.83 ± 0.2) and preexisting proteinuria.

BACKGROUND AND PURPOSE: Upper motor neuron degeneration varies in different phenotypes of MND. We used single-voxel MR spectroscopy of the primary motor cortex to detect corticomotoneuron degeneration and glial hyperactivity in different phenotypes of MND with a relatively short disease duration, contributing to further delineation of the phenotypes. MATERIALS AND METHODS: We prospectively included patients with ALS-B, ALS-L, and PMA and compared their data with those of patients with PLS and healthy controls. Each cohort consisted of 12 individuals. Disease duration was

Background Angiogenesis inhibition is a rational treatment strategy for high-grade glioma (HGG). Combined antiangiogenic therapy and chemotherapy could be beneficial, taking advantage of different mechanisms of antitumour activity of both therapies. We carried out a phase I–II clinical trial with the combination of bevacizumab and continuous dose-intense temozolomide (TMZ) for patients with a recurrent HGG after first- or second-line treatment. Patients and methods Twenty-three HGG patients were treated with bevacizumab (10 mg/kg i.v. every 3 weeks) and TMZ (daily 50 mg/m2), until clinical or radiological progression. Conventional and dynamic magnetic resonance imaging (MRI) were carried out on days -4, 3 and 21 and until clinical or radiological progression. Results Overall response rate (20%), 6-month progression-free survival (PFS6) (17.4%), median progression-free survival (13.9 weeks) and median overall survival (OS) (17.1 weeks) were considerably lower compared with most other studies with bevacizumab-containing regimens. The dynamic MRI parameters contrast transfer coefficient and relative cerebral blood volume decreased rapidly during the early phases of treatment, reflecting changes in vascularisation and vessel permeability but not in tumour activity. In addition, >50% of patients showed oedema reduction and a reduced shift on T1 images. Conclusion Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.

PURPOSE: To analyze the distribution of different shapes of time-intensity curves (TICs) in synovial tissue of patients with rheumatoid arthritis (RA) and to compare relative numbers of TIC shapes between patients with RA and healthy control subjects. MATERIALS AND METHODS: This prospective study was approved by the institutional review board; patients and control subjects gave written informed consent. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the knee joint in five patients with early RA and in five control subjects was performed. Parametric maps showing seven TIC shape types were created. Spatial information of the synovial TIC shape distribution pattern and relative number of TIC shapes were calculated on a three-dimensional region of interest. Relative TIC shape numbers were compared by using a nonparametric Mann-Whitney U test. RESULTS: Synovial enhancement in patients with RA consisted of type 2 TIC shapes (slow enhancement) with heterogeneous zones of types 3 (fast enhancement followed by plateau phase), 4 (fast enhancement followed by early washout phase), and 5 (fast enhancement followed by slow enhancement increase) TIC shapes, compared with almost only type 2 TIC shapes in control subjects. The heterogeneous zones were seen in the lateral and medial knee compartments and around the cruciate ligaments. A significantly higher relative number of type 4 TIC shapes was observed in the patient group compared with the control group (16.5% vs 6.9%, P = .008). CONCLUSION: The pixel-by-pixel dynamic contrast-enhanced MR imaging TIC shape analysis may help distinguish patients with RA from control subjects on the basis of the relative number of type 4 TIC shapes. This study provides the rationale for future research to evaluate the utility of this approach in clinical practice

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.

BackgroundNeurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these.AimsTo assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study.MethodEffects of ecstasy and other substances were assessed with1H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [123I]2β-carbomethoxy-3β-(4-iodophenyl)-tropane ([123I]β-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses.ResultsEcstasy showed specific effects in the thalamus with decreased [123I]β-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients.ConclusionsConverging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

We are reporting on a case of complex lesion of the popliteal neurovascular bundle in a young woman, resulting from an operation for reduction and synthesis of a closed spiroid fracture of the mid-distal third of the left tibia by means of a Grosse-Kempf nail, with significant delay of clinical manifestation. Determining whether this is an "unavoidable complication" or "medical malpractice" is the target of the forensic investigation. In this case, the investigation leads to the conclusion that medical malpractice was the only explanation of the damage.

Dynamic contrast enhanced (DCE) MRI is a widespread method that has found broad application in the imaging of the musculoskeletal (MSK) system. A common way of analyzing DCE MRI images is to look at the shape of the time-intensity curve (TIC) in pixels selected after drawing an ROI in a highly enhanced area. Although often applied to a number of MSK affections, shape analysis has so far not led to a unanimous correlation between these TIC patterns and pathology. We hypothesize that this might be a result of the subjective ROI approach. To overcome the shortcomings of the ROI approach (sampling error and interuser variability, among others), we created a method for a fast and simple classification of DCE MRI where time-curve enhancement shapes are classified pixel by pixel according to their shape. The result of the analysis is rendered in multislice, 2D color-coded images. With this approach, we show not only that differences on a short distance range of the TIC patterns are significant and cannot be appreciated with a conventional ROI analysis but also that the information that shape maps and conventional standard DCE MRI parameter maps convey are substantially different.

Purpose To prospectively compare three strategies of magnetic resonance colonography (MRC) with fecal tagging. Materials and Methods Three strategies were compared: (S1) gadolinium as oral tagging agent and a gadolinium-water mixture for rectal filling (bright lumen), (S2) oral barium and water rectally, and (S3) oral barium and air rectally. In S2 and S3 (both dark lumen) gadolinium was injected intravenously. Three-dimensional (3D) T1-weighted and two-dimensional (2D) T2-weighted sequences were used. Two observers scored diagnostic confidence and image quality (contrast, homogeneity, artifacts), analyzed by chi-squared and Fisher's exact test. Patient experience and preference were determined by questionnaire (Mann-Whitney test). Results A total of 45 patients were included, 15 were randomly assigned per strategy. Diagnostic confidence of S1 and S3 is significantly better than for S2. S1 has the additional advantage of showing significantly better contrast between bowel wall and lumen, and showing significantly better homogeneity on both T1- and T2-weighted sequences, but with significantly more artifacts on the T1-weighted sequences. S3 showed significantly better contrast and homogeneity than S2 on the T2-weighted sequences. Bowel preparation of S1 was rated significantly better. Patient preference was comparable. Conclusion Image quality was best using the bright lumen strategy or the dark lumen strategy using air for rectal filling. Although bowel preparation was rated best using the bright lumen strategy, patient preference was comparable. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.

Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs).Forty-seven patients with early arthritis (arthritis duration1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs.The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve ).These results suggest that the K(trans) , kep , and ve can be used to detect synovial inflammation in patients with early arthritis, and these PKM parameters may be helpful in differential diagnosis. This approach may also be useful in translational research analyzing tissue microcirculation and angiogenesis.

To compare the between-session reproducibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with time-intensity curve (TIC)-shape analysis in arthritis patients, within one scanner and between two different scanners, and to compare this method with qualitative analysis and pharmacokinetic modeling (PKM).Fifteen knee joint arthritis patients were included and scanned twice on a closed-bore 1.5T scanner (n = 9, group 1), or on a closed-bore 1.5T and on an open-bore 1.0T scanner (n = 6, group 2). DCE-MRI data were postprocessed using in-house developed software ("Dynamo"). Disease activity was assessed.Disease activity was comparable between the two visits. In group 1 qualitative analysis showed the highest reproducibility with intraclass correlation coefficients (ICCs) between 0.78 and 0.98 and root mean square-coefficients of variation (RMS-CoV) of 8.0%-14.9%. TIC-shape analysis showed a slightly lower reproducibility with similar ICCs (0.78-0.97) but higher RMS-CoV (18.3%-42.9%). The PKM analysis showed the lowest reproducibility with ICCs between 0.39 and 0.64 (RMS-CoV 21.5%-51.9%). In group 2 TIC-shape analysis of the two most important TIC-shape types showed the highest reproducibility with ICCs of 0.78 and 0.71 (RMS-CoV 29.8% and 59.4%) and outperformed the reproducibility of the most important qualitative parameter (ICC 0.31, RMS-CoV 45.1%) and the within-scanner reproducibility of PKM analysis.TIC-shape analysis is a robust postprocessing method within one scanner, almost as reproducible as the qualitative analysis. Between scanners, the reproducibility of the most important TIC-shapes outperform that of the most important qualitative parameter and the within-scanner reproducibility of PKM analysis.

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p

Purpose To determine whether abdominal 3.0T MRI can be used for evaluation of Crohn's disease (CD) compared with ileocolonoscopy (CS), and to determine patient preference for MRI as opposed to CS. Materials and Methods Twenty patients scheduled for CS underwent MRI. At CS, disease severity was graded and the Crohn's Disease Endoscopic Index of Severity (CDEIS) was determined. Radiological grading (by two observers) was compared with endoscopic grading and CDEIS. Patient experience and preference were determined. Results In respectively 10 (observer 1) and 13 patients (observer 2) exact agreement between radiological and endoscopic grading was found. In respectively 10 and 7 patients radiological and endoscopic grading differed one level. No statistically significant correlation was found between radiological grading and CDEIS. Between bowel wall thickness and CDEIS weak to moderate correlations were found, and between bowel wall enhancement and CDEIS weak correlations were found. All patients preferred MRI over CS. Conclusion It is feasible to perform abdominal 3.0T MRI using orally administered contrast medium for evaluation of CD, and this method can be considered a patient-friendly alternative to CS. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Proximal humeral fractures are complex lesions with difficult management problems; therefore, they pose a challenge for orthopaedic surgeons. In the literature, numerous treatment techniques have been proposed for these kinds of fractures. In our study we reviewed 30 patients with a mean age of 75 years presenting a proximal humeral fracture (Neer 2-3) and treated at our clinic with a Polarus nail, with a mean follow-up of 7 years. We obtained 73.3% of good and excellent results in line with literature. Complications were recorded in 6 of the patients (20%) recruited in our study. In particular, 3 cases of proximal screw pull-out, 1 case of deep infection and 2 cases of acromio-clavicular joint impingement syndrome. The aim of our study was to review our case histories and compare them with the literature analysing this complex type fracture and treatment options.

To compare DCE-MRI parameters and the relative number of time–intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients. DCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (n = 43) and inactive disease (n = 34). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (K trans), extravascular space fractional volume (V e) and reverse volume transfer constant (k ep) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane. Imaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036). The pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC. • The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure

Fractures that involve the distal area of the tibia are associated with a high percentage of complications. Soft tissue oedema, swelling, blisters, skin abrasions and open wounds could compromise the outcome of these lesions. The waiting time before surgery with ORIF is mostly due to soft tissue conditions. Early application of a simple joint-spanning external fixator would achieve the initial goal of stability and the respect of soft tissue, thereby decreasing the time necessary for definitive treatment. A total of 40 consecutive patients (22 male and 18 female) with a mean age of 52 years (range 17-82 years) with distal tibial fracture treated between January 2010 and January 2013 were evaluated. Early temporary external fixation was the first treatment step. Twenty patients had pilon fractures, characterised by the intra-articular involvement of the distal tibia with metaphyseal extension, and 20 patients had malleolar fracture-dislocation. Patients were divided into two groups, A and B. Group A comprised 10 patients with ankle fracture-dislocation and bone fragmentation, who were treated with a temporary bridging external fixation that was maintained after ORIF to exploit ligamentotaxis during the first phases of bone healing. In Group B (30 patients), the external fixation was removed after ORIF. The results of the study are in line with the recent literature: temporary external fixation in high-energy trauma and fracture-dislocation of the ankle enables soft tissue to be restored, which facilitates postoperative assessment of bone fragments by CT scan. The complication rate in this study was 5% in patients with malleolar fractures and 20% in patients with pilon fractures. The maintenance of temporary external fixation after ORIF synthesis during the entire first stage of bone healing seems to be a good method of treatment that has a low rate of soft tissue complications.

An Orthofix® monolateral axial external fixator was used to treat 31 patients with non-union of the humeral shaft, 30 of whom had been previously treated surgically. In seven cases the non-union was hypertrophic and one of these cases had been treated by simple fixation anol compression, the others by fixation, bone grafting and decortication; in 20 cases the non-union was hypotrophic and had been treated by fixation and decortication with bone grafting. The remaining four cases had septic non-union, treated by debridement of the focus of infection and fixation, followed in three cases by a bone graft and osteomuscular decortication once the infection had been eradicated. The fracture site consolidated in all patients in a mean time of 4.9 months. Five patients required further surgery: three in the group with infected non-union and two who had had a new bone graft and application of the external fixator, one because of a refracture (the patient was receiving chronic treatment with antimitotic agents) and one because of persistent non-union. There were no major complications (e.g. radial nerve palsy, joint stiffness, deep infection), and only six cases of pin track infection (5% of the screws implanted). The authors believe that this method is reliable, effective and low risk provided that the patient is cooperative; furthermore, the monolateral axial external fixator is tolerated well and allows movement of the shoulder and elbow throughout the period of treatment.

To prospectively compare conventional MRI sequences, dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging (DWI) with histopathology of surgical specimens in Crohn's disease. 3-T MR enterography was performed in consecutive Crohn's disease patients scheduled for surgery within 4 weeks. One to four sections of interest per patient were chosen for analysis. Evaluated parameters included mural thickness, T1 ratio, T2 ratio; on DCE-MRI maximum enhancement (ME), initial slope of increase (ISI), time-to-peak (TTP); and on DWI apparent diffusion coefficient (ADC). These were compared with location-matched histopathological grading of inflammation (AIS) and fibrosis (FS) using Spearman correlation, Kruskal-Wallis and Chi-squared tests. Twenty patients (mean age 38 years, 12 female) were included and 50 sections (35 terminal ileum, 11 ascending colon, 2 transverse colon, 2 descending colon) were matched to AIS and FS. Mural thickness, T1 ratio, T2 ratio, ME and ISI correlated significantly with AIS, with moderate correlation (r = 0.634, 0.392, 0.485, 0.509, 0.525, respectively; all P

The objective of our study was to perform a semiquantitative analysis of dynamic contrast-enhanced MRI for the evaluation of disease activity and therapeutic response in patients with perianal fistulizing Crohn disease. Sixteen consecutively registered patients with perianal Crohn disease underwent pelvic MRI. A dynamic contrast-enhanced sequence was performed at 3 T (temporal resolution, 4.2 seconds) during i.v. contrast injection. Maximum enhancement, initial slope of increase, volume transfer constant (K(trans)), and the extravascular space fractional volume (x028B;(e)) were calculated in a region of interest drawn around the fistula. Perianal disease activity index, C-reactive protein concentration, and an MRI-based activity score were calculated as reference standards. Six patients underwent a second MRI examination 6 weeks after starting treatment with anti-tumor necrosis factor α (anti-TNF-α). Perianal disease activity index moderately correlated with maximum enhancement (r = 0.67, p = 0.005), initial slope of increase (r = 0.58, p = 0.018), and volume of enhancing pixels (r = 0.79, p < 0.001) but not with K(trans) or x028B;(e). Volume of enhancing pixels also correlated with C-reactive protein concentration and the MRI-based score (r = 0.52, p = 0.041; r = 0.79, p < 0.001). The K(trans) values had decreased significantly 6 weeks after the start of anti-TNF-α therapy. Maximum enhancement and initial slope of increase correlate with disease activity in perianal Crohn disease. K(trans) may be an indicator of the effect of therapy on patients starting anti-TNF-α treatment

Objective. Dynamic contrast-enhanced (DCE-MRI) time-intensity curve (TIC) shape analysis has previous- ly been used in oncology, where fast initial enhancement and early washout are associated with malig- nancy. As RA synovium has some tumour-like features, we investigated DCE-MRI TIC shape expression in early arthritis in relationship to diagnosis. Methods. Twenty-eight DMARD-naive, early arthritis patients (

OBJECTIVE: People with velo-cardio-facial syndrome or 22q11 deletion syndrome (22q11DS) have behavioral, cognitive and psychiatric problems. Approximately 30% of affected individuals develop schizophrenia-like psychosis. Glutamate dysfunction is thought to play a crucial role in schizophrenia. However, it is unknown if and how the glutamate system is altered in 22q11DS. People with 22q11DS are vulnerable for haploinsufficiency of PRODH, a gene that codes for an enzyme converting proline into glutamate. Therefore, it can be hypothesized that glutamatergic abnormalities may be present in 22q11DS. METHOD: We employed proton magnetic resonance spectroscopy ((1)H-MRS) to quantify glutamate and other neurometabolites in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of 22 adults with 22q11DS (22q11DS SCZ+) and without (22q11DS SCZ-) schizophrenia and 23 age-matched healthy controls. Also, plasma proline levels were determined in the 22q11DS group. RESULTS: We found significantly increased concentrations of glutamate and myo-inositol in the hippocampal region of 22q11DS SCZ+ compared to 22q11DS SCZ-. There were no significant differences in levels of plasma proline between 22q11DS SCZ+ and 22q11DS SCZ-. There was no relationship between plasma proline and cerebral glutamate in 22q11DS. CONCLUSION: This is the first in vivo(1)H-MRS study in 22q11DS. Our results suggest vulnerability of the hippocampus in the psychopathology of 22q11DS SCZ+. Altered hippocampal glutamate and myo-inositol metabolism may partially explain the psychotic symptoms and cognitive impairments seen in this group of patients.

Objective: The aim of this observational study, promoted by the Health Authorities of the Regione Veneto (Italy), is to assess the prevalence of the most relevant environmental and individual risk factors in subjects with a recent hip fracture. Methods: Patients aged more than 60 years of both genders with a recent hip fracture not associated with malignancies, were administered questionnaires on dietary habits, sun exposure, and disability score. A complete family, pharmacological and pathology history was collected together with information on previous falls, details of the fracture index, and anthropometric data. In all subjects, blood was taken for the measurement of serum 25 hydroxy-vitamin D (25OHD). Results: The study included 704 patients (573 women and 131 men). Mean age was 81±8 years (range 60-102). Severe pre-fracture disability was a common feature (58%) associated with multiple co-morbidities (84%), more frequently cardio- vascular and neurological diseases, and specific medications. In a large proportion (86%) of the patients, environmental or individual risk factors for falling were found. Vitamin D insufficiency (serum 25OHD levels

The authors report their experience in the treatment of the diaphyseal tibial fractures, using the unilateral radiolucent External Fixator (EF) XCaliber.A total of 100 patients (average age 35 years, range 16-76) with 103 displaced diaphyseal tibial fractures were treated with the XCaliber. There were 59 type A fractures, 35 type B, and 9 type C (according to the AO classification) and 35 were open fractures.During the last assessment, patients were evaluated for level of pain, ability to perform weight-bearing activities, and number of residual deformities.The average follow-up time was 24 months, 3 patients (4 fractures) were excluded for final assessment and 1 patient moved abroad. Of the remaining 98 fractures, 83 (84.7%) healed with a single operation in a mean 21 weeks (SD 3.97; 12-38 weeks), 10 fractures had a delayed union and 5 fractures proceeded to a non-union. There were 13 complications. Among them, a loss of reduction was observed in 3 cases due to overload of the EF, in 3 cases, deep pin track infections were observed and 2 fractures healed with more than 1 cm of shortening.The results are encouraging, since both complex and open fractures were included in this study. The XCaliber was shown to be a valid unilateral external fixator, combining the advantage of radiolucency during application and radioscopic follow-up with a stable and flexible fracture fixation. This represents the first report in the literature specifically examining treatment of tibial diaphyseal fractures with a radiolucent external fixator.

Purpose: To prospectively determine clinical value of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the evaluation of disease activity in perianal Crohn disease (CD). Materials and Methods: Patients provided written informed consent. Study approval was waived by an institutional review board. Thirty-three patients with perianal CD underwent pelvic MR imaging; 17 were male (mean age, 37.4 years +/- 10.8 [standard deviation]; age range, 18-54 years) and 16 were female (mean age, 32.0 years +/- 8.3; age range, 16-43 years). Dynamic contrast-enhanced MR imaging was performed; time-intensity curves (TICs) were obtained. Each pixel was classified as one of six predefined TIC shape types. For each MR imaging examination, a region of interest (ROI) was drawn around the fistula on the single section corresponding to the most extensive and most hyperintense lesion; maximum enhancement (ME), slope of enhancement, and TIC shapes were calculated. Absolute and relative numbers of pixels for each curve type were calculated in a two-dimensional ROI. These results were compared with Perianal Disease Activity Index (PDAI),C-reactive protein (CRP) level, an MR imaging-based severity score, and clinical outcome. A Spearman rank correlation test was used to calculate correlation coefficients between dynamic contrast-enhanced MR imaging parameters and reference parameters. A Mann-Whitney U test was used to calculate differences in dynamic contrast-enhanced MR imaging parameters between predefined groups of patients. Results: Significant correlations were found between the absolute amounts of the TIC shape types and PDAI and between ROI volume and PDAI. The ratio of quickly enhancing versus slowly enhancing pixels correlated with higher MR imaging scores as did the ROI volume. The absolute amounts of pixels displaying TIC types 2, 3, 4, and 5 correlated significantly with MR imaging score. CRP level showed a significant correlation with mean ME. Larger numbers of quickly enhancing pixels were observed in patients who needed medication changes or developed new abscesses during follow-up. Conclusion: Dynamic contrast-enhanced MR imaging can help determine disease activity in perianal CD and might be helpful in selecting a subpopulation of patients who should be monitored more closely for development of more extensive disease

SUMMARY: Arterial spin-labeling (ASL) is a relatively new and noninvasive MR imaging technique, used to measure cerebral blood flow (CBF). Scanning time and reproducibility remain important issues in the clinical applicability of ASL. We expected both to benefit from higher field strengths. We describe that when performing ASL at 3T, 20 averages suffice to obtain steady and reproducible CBF values. Scanning time can be as short as 3 minutes.

Purpose To determine the feasibility of T1-mapping and calculation of Gadolinium-values in luminal Crohn's Disease (CD). Materials and Methods Nine patients with active CD were included. For each patient disease activity was determined, based on endoscopic and histopathological results. The Crohn's Disease Endoscopic Index of Severity (CDEIS), the Harvey-Bradshaw index (HBI) and C-reactive protein (CRP) were also determined as reference standards. T1-measurements were performed before and after intravenous administration of Gadodiamide in 14 slices in a single breath-hold using the Look-Locker (LL) sequence in combination with a segmented three-dimensional Turbo Field Echo sequence. A Region of Interest (ROI) was drawn around inflamed bowel loops and the mean Gadolinium-concentration within the ROI was calculated. Gadolinium-concentrations were compared between patients with mild and marked disease, as determined by the reference standards. Results Mean Gadolinium-concentrations were higher in bowel loops of patients with more active disease, as defined by endoscopic and histopathological examination, CRP, and HBI. Conclusion By using a breath-hold LL sequence in the bowel quantitative assessment of contrast agent concentration is possible, thus permitting objective evaluation of physiological changes in actively inflamed tissue in an area that suffers from motion problems. J. Magn. Reson. Imaging 2009;29:488–493. © 2009 Wiley-Liss, Inc.

Dynamic contrast enhanced (DCE) MRI is widely acknowledged to be a helpful tool in the diagnosis and differentiation of tumors. In common clinical settings, the dynamic changes described by the time–intensity curves (TICs) are evaluated to find patterns of atypical tissue behavior, i.e., areas characterized by rapid contrast wash-in and wash-out. Despite the ease of this approach, there is no consensus about the specificity of the TIC shapes in discriminating tumor grades. We explore a new way of looking at TICs, where these are not averaged over a selected region of interest (ROI), but rendered pixel-by-pixel. In this way, the characteristic of the tissue is not given as a single TIC classification but as a distribution of the different TIC patterns. We applied this method in a group of patients with chondroid tumors and compared its outcome with the outcome of the standard ROI-based averaged TIC analysis. Furthermore, we focused on the problem of ROI selection in these tumors and how this affects the outcome of the TIC analysis. Finally, we investigated what relationship exists between the “standard” DCE-MRI parameter maximum enhancement (ME) and the TIC shape. Conclusions We demonstrate that, where the ROI approach fails to show the presence of areas of rapid contrast wash-in and wash-out, the pixel-by-pixel approach reveals the coexistence of a heterogeneous pattern of TIC shapes. Secondly, we point out the differences in the DCE MRI parameters and tumor volume that can result when selecting the tumor based on DCE parameter maps or post-contrast T1-weighted images. Finally, we show that ME maps and TIC shape maps highlight different tissue areas and, therefore, the use of the ME maps is not appropriate for the correct identification of areas of atypical TICs.

Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy). Results In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of de novo aneurysm formation, the incidence of subarachnoid hemorrhage (SAH), and the growth of existing untreated aneurysms in 52 patients after therapeutic carotid artery balloon occlusion for carotid aneurysms. PATIENTS AND METHODS: Between January 1996 and August 2004, 52 patients were treated with carotid artery balloon occlusion for carotid aneurysms. In June 2005, all patients, their next of kin, or family physicians were contacted and questioned concerning episodes of headache or hospital admissions that could be attributed to SAH. In addition, MR imaging and MR angiography (MRA) at 3T were performed in 26 of 44 surviving patients after a mean follow-up period of 50.2 months (median, 43.5 months; range, 14–107 months). MR imaging and MRA studies were compared with the digital subtraction angiograms at the time of carotid artery occlusion. RESULTS: During clinical follow-up of 52 patients at a mean of 50.3 months (median, 42.5 months; range, 0–107 months), no episodes of SAH were reported (0%; 97.5% confidence interval [CI], 0–8.2%). In the 26 patients with follow-up MR imaging, no de novo aneurysms were detected (0%; 97.5 CI, 0–13.2%). Five existing untreated small aneurysms in 5 patients had not enlarged after a mean follow-up of 40 months. CONCLUSION: In this study, therapeutic carotid artery occlusion was not associated with development of new aneurysms or enlargement of existing untreated aneurysms with time.

OBJECTIVE: The purpose of this study was to evaluate aneurysm size and clinical symptoms midterm after therapeutic carotid artery occlusion in 39 patients with large or giant carotid artery aneurysms. METHODS: Between January 1996 and August 2004, 39 patients with large or giant carotid artery aneurysms were treated with therapeutic carotid artery occlusion and had clinical and magnetic resonance imaging follow-up of at least 3 months (mean, 35.9 mo; median, 29 mo; range, 3-107 mo; 117 patient-yr). Initial clinical presentation was mass effect caused by the aneurysm in 32 (82%) of the 39 patients. Three patients presented with subarachnoid hemorrhage and one presented with epistaxis; two aneurysms were an incidental finding and one was additional to another ruptured aneurysm. RESULTS: There were no early or late complications of therapeutic carotid artery occlusion. All aneurysms seemed to have thrombosed completely after carotid artery occlusion as observed on early and late magnetic resonance imaging and magnetic resonance angiographic follow-up studies. At the time of the most recent magnetic resonance imaging follow-up study, 29 (74%) of the 39 aneurysms involuted totally, two aneurysms decreased to 25% of the original diameter, two aneurysms decreased to 50%, and five aneurysms decreased to 75%. Two aneurysms remained unchanged in size after 49 and 58 months, respectively. At the most recent clinical follow-up evaluation, symptoms of mass effect were cured in 19 (60%), improved in 10 (31%), and remained unchanged in three (9%) of the 32 patients. CONCLUSION: Therapeutic carotid artery occlusion was a simple, safe, and effective treatment for large and giant carotid artery aneurysms. Almost all aneurysms involute completely or substantially decrease in size. Alleviation of symptoms of mass effect was achieved in most patients.

Minimally invasive diagnostic techniques would be useful in the preoperative diagnosis of patients with hypertension and ischemic renal disease. The aim of our study was to compare color Doppler sonography (CDS), and magnetic resonance angiography (MRA) with the reference standard, digital subtraction angiography (DSA), in the diagnosis of renal artery stenosis.Thirty-nine patients with arterial hypertension and monolateral or bilateral renal artery stenosis documented by CDS underwent renal artery MRA and then DSA during corrective percutaneous transluminal angioplasty. CDS and MRA scans were evaluated by 3 independent observers who studied 78 main renal arteries. Stenosis of 70% or more were regarded as significant. Sensitivity, specificity, positive and negative predictive values and two-sided 95% confidence intervals of CDS and MRA for the detection of significant renal artery stenosis were calculated. The statistical significance of the differences in sensitivities between CDS and MRA was assessed by means of the kappa test (or =1).CDS and MRA, therefore, both achieved 97.6% sensitivity and 100% specificity for diagnosing stenoses at the origin of the renal artery; CDS yielded 100% sensitivity and 97.1% specificity and MRA 87.5% sensitivity and 98.6% specificity for diagnosing stenosis in the intermediate distal segments.Statistically significant differences between CDS and MRA in the diagnosis of renal artery stenosis have not been observed. However, according to our experience, CDS is the preferred technique because it also provides useful information about the development of kidney disease before correction.

BACKGROUND AND PURPOSE: Digital subtraction angiography (DSA) is used to follow-up intracranial aneurysms treated with detachable coils to identify recurrence and determine need for additional treatment. However, DSA is invasive and involves a small risk of neurologic complications. We assessed the feasibility and usefulness of 3D time-of-flight (TOF) MR angiography (MRA) performed at 3T compared with DSA for the follow-up of coil-treated intracranial aneurysms. METHODS: In a prospective study, 20 consecutive patients with 21 intracranial aneurysms treated with coils underwent DSA and nonenhanced and enhanced multiple overlapping thin-slab acquisition 3D TOF MRA at 3T on the same day at a mean follow-up of 6 months (range, 4–14 months) after coil placement. MRA images were evaluated for presence of artifacts, presence and size of aneurysm remnants and recurrences, patency of parent and branch vessels, and added value of contrast material enhancement. MRA and DSA findings were compared. RESULTS: Interobserver agreement of MRA was good, as was agreement between MRA and DSA. All three recurrences that needed additional treatment were detected with MRA. Minor disagreement occurred in four cases: three coil-treated aneurysms were scored on MRA images as having a small remnant, whereas on DSA images these aneurysms were occluded; the other aneurysm was scored on MRA images as having a small remnant, whereas on DSA images this was a small recurrence. Use of contrast material had no additional value. Coil-related MR imaging artifacts were minimal and did not interfere with evaluation of the occlusion status of the aneurysm. CONCLUSION: High-spatial-resolution 3D TOF MRA at 3T is feasible and useful in the follow-up of patients with intracranial aneurysms treated with coil placement.

Background Renal artery stenosis (RAS) is a known cause of hypertension and ischemic nephropathy. Stenting of the artery is a valid approach, in spite of cases of unexpected adverse evolution of renal function. Methods In this study, 27 patients with unilateral RAS were subjected to stenting and followed for a period of one year, while 19 patients were observed while on medical treatment only. The group of 27 patients, 67.33 ± 6.8 years of age, creatinine of 2.15 ± 0.9 mg/dl, following stenting, were followed at intervals with biochemical tests, renal scintigraphy and doppler ultrasonography. The control group (70.0 ± 6.1 years, creatinine 1.99 ± 0.7 mg/dl) was also followed for one year. Result One year after stenting mean creatinine clearance (Ccr) increased from 36.07 ± 17.2 to 40.4 ± 21.6 ml/min (NS). Arterial BP, decreased after 1,3,6, and 12 months (p < 0.05). The number of antihypertensive drugs also decreased (p < 0.05). A significant increase in proteinuria was also observed. In the control group both Ccr, BP and proteinuria did not show significant changes. Based on renal scintigraphy and Ccr at subsequent times, it was possibile to evaluate the timecourse of renal function in both kidneys of the stented patients. In the stented kidneys Ccr increased significantly. On the controlateral kidney a decrease of renal function (p < 0.05) was observed. Resistance index appeared to be a risk factor of the functional outcome. Conclusions Stenting of RAS due to atherosclerosis is followed by stabilization or improvement of Ccr, mainly at the stented kidney, while contralateral renal function showed a decrease.

An abscess associated with an intrathoracic goiter is an extremely rare condition. The authors report a case of a thyroid abscess complicated by acute dyspnea and asphyxia in a patient of geriatric age with a substernal goiter. Surgical therapy was necessary to obtain a correct diagnosis and an effective treatment.