Pretreatment evaluation of microcirculation by dynamic contrast-enhanced magnetic resonance imaging predicts survival in primary rectal cancer patients.

PURPOSE: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. METHODS AND MATERIALS: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T1 mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration-time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. RESULTS: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). CONCLUSIONS: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

Evaluation of liver fat in the presence of iron with MRI using T2* correction: a clinical approach.

OBJECTIVES: To assess magnetic resonance imaging (MRI) with conventional chemical shift-based sequences with and without T2* correction for the evaluation of steatosis hepatitis (SH) in the presence of iron. METHODS: Thirty-one patients who underwent MRI and liver biopsy because of clinically suspected diffuse liver disease were retrospectively analysed. The signal intensity (SI) was calculated in co-localised regions of interest (ROIs) using conventional spoiled gradient-echo T1 FLASH in-phase and opposed-phase (IP/OP). T2* relaxation time was recorded in a fat-saturated multi-echo-gradient-echo sequence. The fat fraction (FF) was calculated with non-corrected and T2*-corrected SIs. Results were correlated with liver biopsy. RESULTS: There was significant difference (P < 0.001) between uncorrected and T2* corrected FF in patients with SH and concomitant hepatic iron overload (HIO). Using 5 % as a threshold resulted in eight false negative results with uncorrected FF whereas T2* corrected FF lead to true positive results in 5/8 patients. ROC analysis calculated three threshold values (8.97 %, 5.3 % and 3.92 %) for T2* corrected FF with accuracy 84 %, sensitivity 83-91 % and specificity 63-88 %. CONCLUSIONS: FF with T2* correction is accurate for the diagnosis of hepatic fat in the presence of HIO. Findings of our study suggest the use of IP/OP imaging in combination with T2* correction. KEY POINTS: • Magnetic resonance helps quantify both iron and fat content within the liver • T2* correction helps to predict the correct diagnosis of steatosis hepatitis • "Fat fraction" from T2*-corrected chemical shift-based sequences accurately quantifies hepatic fat • "Fat fraction" without T2* correction underestimates hepatic fat with iron overload.

Effects of deletion and duplication in a patient with a 46,XX,der(7)t(7;17)(q36;p13)mat karyotype.

Exact breakpoint determination by DNA-array has dramatically improved the analysis of genotype-phenotype correlations in chromosome aberrations. It allows a more exact definition of the most relevant genes and particularly their isolated or combined impact on the phenotype in an unbalanced state. Here, we report on a 21-year-old female with severe growth retardation, severe intellectual disability, hypoplasia of the corpus callosum, unilateral sacral hypoplasia, tethered cord, various minor facial dysmorphisms, and a telomeric deletion of about 4.4 Mb in 7q36.2->qter combined with a telomeric duplication of about 8 Mb in 17pter->p13.1. Fine mapping was achieved with the Illumina® Infinium HumanOmni1-Quad v1.0 BeadChip. Most of the major clinical features correspond to the well-known effects of haploinsufficiency of the MNX1 and SHH genes. In addition, review of the literature suggests an association of the 17p duplication with specific facial dysmorphic features and skeletal anomalies, but also an aggravating effect of the duplication-deletion for severe growth retardation as well as sacral and corpus callosum hypoplasia by one or more genes located on the proximal half of the segmental 17p duplication could be elaborated by comparison with other patients from the literature carrying either the deletion or the duplication found in our patient.

Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions.

A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT.

Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis.

PURPOSE: To describe details about the implementation of a dynamic T(1)-mapping technique and a simple data analysis strategy that can be used to predict therapy outcome in primary rectal carcinoma and to investigate the physiologic meaning of the obtained parameter. MATERIALS AND METHODS: Contrast-enhanced dynamic T(1) mapping was achieved with a snapshot fast low-angle shot (FLASH) T(1) mapping sequence implemented on a 1.5 T MR scanner. This method was applied to 58 patients with primary rectal cancer before onset of chemoradiation therapy. A simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration-time curve divided by the maximum of the arterial input function (AIF) was used as a measure of tumor microcirculation (PI values). RESULTS: The snapshot FLASH (SFL) T(1)-mapping technique is accurate and sensitive enough to detect inhomogeneous uptake kinetics within tumor tissue. Classifying the patients into two groups according to therapy response showed lower mean PI values for responders as compared to nonresponders. PI was found to combine information about permeability surface area product (PS) and blood volume. CONCLUSIONS: The described method based on dynamic T(1) mapping has the potential to be a clinical tool for predicting therapy outcome of preoperative chemoradiation in patients with primary rectal carcinoma.

Efficacy and safety of gadodiamide (Gd-DTPA-BMA) in renal 3D-magnetic resonance angiography (MRA): a phase II study.

PURPOSE: To determine the most efficacious dose of gadodiamide for three-dimensional (3D) contrast-enhanced (CE) magnetic resonance angiography (MRA) of the renal arteries on a patient level based on the sensitivity in detecting the main hemodynamically relevant (> or =50% or occlusion) renal artery stenosis (RAS) using intra-arterial digital subtraction angiography (IA DSA) as the gold standard. MATERIALS AND METHODS: This prospective, randomized, double-blind, parallel-group, multicenter study included 273 patients referred to IA DSA for suspected RAS. Patients underwent 3D CE MRA after injection of 0.01, 0.05, 0.1, or 0.2mmol/kg of body weight gadodiamide (0.5mmol/ml). The images were assessed for location and degree of RAS by independent blinded readers (MRA: three readers, IA DSA: one reader). Hypothesis testing for a significant trend in sensitivity across dose groups was based on the one-sided Cochran-Armitage style trend test for each independent MRA reader. RESULTS: The lowest dose group (0.01mmol/kg) proved non-efficacious in detecting hemodynamically relevant (i.e., > or =50% or occlusion) RAS. A statistically significant dose trend (p<0.001) was shown for each of the three independent readers. Depending on reader, the sensitivity obtained with 0.05, 0.1, and 0.2mmol/kg was 63.9-86.1%, 75.8-91.4% and 80.6-90.6%, the specificity was 66.7-73.9%, 59.3-75.0%, and 59.3-75.0% and accuracy was 67.8-78.9%, 75.4-77.4%, and 76.3-81.0%, for the three dose groups, respectively. There were eight non-severe adverse events (AEs). Three serious AEs occurring in one patient were judged not related to gadodiamide by the on-site investigator. CONCLUSION: A significant dose trend between the four doses examined was observed. The lowest dose (0.01mmol/kg) differed significantly from those of the other three doses. Based on the analysis of the primary and secondary endpoints, 0.1mmol/kg gadodiamide appears to be the most suitable dose in diagnosing hemodynamically relevant RAS. The present study also demonstrated gadodiamide to be safe and well tolerated.

Remitting seronegative symmetrical synovitis with pitting edema of the hands: ultrasound, color doppler ultrasound, and magnetic resonance imaging findings.

OBJECTIVE: To assess the value of gray-scale ultrasound (US), color Doppler ultrasound (CDUS), contrast-enhanced CDUS, and magnetic resonance imaging (MRI) in the diagnostic evaluation of the hands in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE). METHODS: Eight patients (5 men, 3 women; mean +/- SD age 69.3 +/- 7.2 years) with clinical diagnosis of RS3PE syndrome underwent US, CDUS, contrast-enhanced CDUS, and MRI. US was performed with a linear array transducer operating at 12 MHz. The US contrast agent (SHU 508; Levovist, Schering, Germany) was intravenously infused in a concentration of 300 mg/ml at a rate of 1 ml/minute. RESULTS: All patients showed symmetric subcutaneous edema and synovitis of tendons and finger joints on both US and MRI. Vascularity was detected subcutaneously in tendon sheaths and in the joint synovia on CDUS and MRI. Detection of increased vascularity was improved after contrast administration compared with unenhanced CDUS (P < 0.01). CONCLUSION: Ultrasound, CDUS, contrast-enhanced CDUS, and MRI are valuable tools in the diagnostic evaluation of involved anatomic structures in patients with RS3PE. Contrast-enhanced CDUS is superior to CDUS in assessment of inflammatory edema, effusion, and synovitis.

Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue.

PURPOSE: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. MATERIALS AND METHODS: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. RESULTS: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g +/- 2.45 versus 3.56 ml/min/100 g +/- 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. CONCLUSION: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated.

Preliminary results on the influence of chemoradiation on apparent diffusion coefficients of primary rectal carcinoma measured by magnetic resonance imaging.

PURPOSE: To study changes of the apparent diffusion coefficient (ADC) measured by magnetic resonance imaging (MRI) in patients with primary rectal carcinoma during a course of combined chemoradiation. PATIENTS AND METHODS: Diffusion-weighted echo-planar imaging at 1.5 T was performed in patients (n = 8) with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation. Mean tumor ADC values and ADC histograms were determined and compared weekly during the course of therapy. Surgical resection of the tumors enabled a correlation of ADC values with the pathologic classification. RESULTS: In four patients tumor T-downstaging (ypT0-2) was observed, and in four patients no downstaging (ypT3) was seen. In all patients, ADC values were higher before onset of chemoradiation therapy compared to the end of chemoradiation. Separating the patients into two groups, a significant increase in ADC value during week 1 of therapy, followed by a steady decrease, was found for the therapy-responder group. In the nonresponder group, no initial increase of ADC values was observed. After the 1st week of therapy, ADC values were significantly lower in the nonresponder group during the remaining duration of therapy. CONCLUSION: With these preliminary results it could be shown that MR diffusion imaging is able to detect individual changes of tumor ADC values during the course of combined chemoradiation reflecting biological changes within the tumor tissue. Further studies will be necessary to prove the possible value of totally noninvasive ADC imaging on predicting therapy outcome.

Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma.

PURPOSE: The aim of our study was to correlate perfusion indices and apparent diffusion coefficients with therapy outcome after chemoradiation. METHODS AND MATERIALS: In 34 patients with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation, pretherapeutic perfusion indices and apparent diffusion coefficients were obtained by dynamic or diffusion-weighted magnetic resonance imaging. Therapy response was defined if the pathologic observation revealed no invasion into the perirectal fat after chemoradiation. RESULTS: In 18 patients, a response and in 16, no response was observed. Statistically significant differences were found for the mean perfusion index (p < 0.001; 7.5 +/- 1.5 mL/min/100 g vs. 10.7 +/- 2.7 mL/min/100 g) and for the intratumoral cumulative fraction of pixels with perfusion-indices > 12 mL/min/100 g (p < 0.001, 3.7 +/- 4.0% vs. 24.7 +/- 17.9%). A three-way ANOVA resulted in significant effects for therapy responder/nonresponder (p < 0.001) and for apparent diffusion coefficient and the individual patients. CONCLUSION: Perfusion indices and apparent diffusion coefficients inside the tumor region seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma. Higher parameter levels in the nonresponding group could be explained by increased shunt flow or increased angiogenic activity in aggressive tumor cell clusters resulting in reduced nutrients supply and higher fraction of intratumoral necrosis respectively.

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE: To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS: Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION: This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.

Investigation of cerebrovascular disease with MR angiography: comparison of volume rendering and maximum intensity projection algorithms--initial assessment.

We assessed the clinical utility of the volume-rendering (VR) algorithm as a postprocessing technique of intracranial magnetic resonance angiography (MRA) for the evaluation of cerebrovascular disease in comparison with the maximum intensity projection (MIP) algorithm. VR and MIP images were compared with digital subtraction angiography (DSA). Volume-rendered views improved the perceptibility of intracranial vasculature and consequently augmented diagnostic confidence, improved the characterization of underlying vascular pathologies, and facilitated image interpretation. Volume rendering has the potential to expand the role of cerebral MRA in the diagnostic investigation and treatment planning of cerebrovascular disease.

Using orbital sonography to diagnose and monitor treatment of acute swelling of the eyelids in pediatric patients.

OBJECTIVE. Clinical signs of acute erythematous swelling of the periorbital region may be related either to benign superficial inflammation or to the more severe and potentially life-threatening condition of orbital infection. CONCLUSION. We recommend orbital sonography in every child with periorbital swelling and erythema. In contrast to superficial infection in which edematous swelling of the eyelid can be documented without lesions of the orbital content, either a hyper- or a hypo-echoic mass displacing the medial rectus muscle laterally is highly suggestive of orbital infection. Introducing sonography into early diagnostic interventions in pediatric patients avoids delaying appropriate treatment and allows disease monitoring on a daily basis.

3D MR angiography of renal arteries: comparison of volume rendering and maximum intensity projection algorithms.

PURPOSE: To compare volume rendering (VR) and maximum intensity projection (MIP) as postprocessing techniques of magnetic resonance (MR) angiography for detection and quantification of renal artery stenosis. MATERIALS AND METHODS: Twenty-seven patients underwent three-dimensional contrast material-enhanced MR angiography of the renal arteries with a 1.5-T imager. For each renal artery, targeted MIP and VR images were reconstructed in oblique coronal and transverse orientations. For each modality, image generation and evaluation were performed interactively by two independent radiologists blinded to angiographic results. In comparison with digital subtraction angiography (DSA) findings, stenosis quantification and detection by using MIP and VR were evaluated with the use of 50% and 70% cutoff points by using linear regression analysis and 2 x 2 tables. Overall image quality and vascular delineation on MIP and VR images were also compared. RESULTS: All main and accessory renal arteries depicted at DSA were also demonstrated on MIP and VR images. VR performed slightly better than MIP for quantification of stenoses greater than 50% (VR: r(2) = 0.84, P <.001; MIP: r(2) = 0.38, P =.001) and significantly better for severe stenoses (VR: r(2) = 0.83, P <.001; MIP: r(2) = 0.21, P =.1). For detection of stenosis, VR yielded a substantial improvement in positive predictive value (VR: 95% and 90%; MIP: 86% and 68% for stenoses greater than 50% and 70%, respectively). Image quality obtained with VR was not significantly better than that with MIP; however, vascular delineation on VR images was significantly better. CONCLUSION: The VR technique of renal MR angiography enabled more accurate detection and quantification of renal artery stenosis than did MIP, with significantly improved vascular delineation.

Finger pulley injuries in extreme rock climbers: depiction with dynamic US.

PURPOSE: To determine the ability of dynamic ultrasonography (US) to depict finger pulley injuries in extreme rock climbers. MATERIALS AND METHODS: Sixty-four extreme rock climbers (climbing levels 8-11 on a scale ranging from 1 to 11; Union Internationale des Associations d'Alpinisme) with finger injuries (75 symptomatic and 181 asymptomatic fingers) were examined by using US, with the transducer operating at 12 MHz. The distance between the flexor tendon and phalanx was evaluated in extension and forced flexion at the level of the A2 and A4 annular pulleys as an indicator of tendon bowstringing. A distance between the flexor tendon and phalanx greater than 1.0 mm was interpreted as positive for a pulley injury. US findings were compared with those of magnetic resonance imaging. Surgical correlation was available in seven cases. Statistical analysis was performed by using analysis of variance, the Student t test, and the Bonferroni method. RESULTS: US depicted 16 (100%) of 16 complete A2 pulley ruptures, nine (100%) of nine complete A4 pulley ruptures, six (86%) of seven surgically proved complete combined A2 and A3 pulley ruptures, and 15 (100%) of 15 incomplete A2 pulley ruptures. Measurement of distance between the flexor tendon and phalanx was significantly different among patient subsets without pulley ruptures and those with incomplete, complete, or complete combined pulley ruptures (P <.001). The sensitivity of US for depiction of finger pulley injuries was 98%, and specificity was 100%. CONCLUSION: Dynamic US allows excellent depiction of finger pulley injuries in extreme rock climbers.

Decreased high-energy phosphate ratios in the myocardium of men with diabetes mellitus type I.

AIMS/HYPOTHESIS: To investigate whether alterations in high-energy phosphates occur in the myocardium of persons with diabetes mellitus type I. Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial high-energy phosphates have been shown to be reduced by ischemia, and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. METHODS: The present study involved 34 male patients (mean age 35.5 +/- 10.1) with diabetes mellitus type I and 35 healthy male volunteers (mean age 36 +/- 8.6) as age-matched controls. Phosphorus-31 magnetic resonance spectroscopic imaging of the heart was performed in all subjects using a 1.5-T whole-body magnetic resonance scanner. The ratios of phosphocreatine (PCr) to beta-adenosinetriphosphate (beta-ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The myocardium of patients with diabetes mellitus type I showed significantly decreased ratios of PCr to beta-ATP compared with healthy controls in the left ventricle (1.90 +/- 0.4 vs. 2.15 +/- 0.3, p < 0.05). We found a moderate negative correlation between the ratio of PCr to beta-ATP in the left ventricle and both, the diastolic left ventricular function (E/A; r = -0.41) and the glycohemoglobin A1c (GHbA1c; r = -0.42). CONCLUSION: This study demonstrates for the first time a decreased ratio of PCr to beta-ATP in the myocardium of persons with diabetes mellitus type I without a known history of coronary heart disease.