Cell motility and migration as determinants of stem cell efficacy.

BACKGROUND: Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells. METHODS: We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including but not limited to migratory potential, trophic factor release and transcriptomic signature. To assess lesion-targeted migration and therapeutic properties of isolated subpopulations in vivo, surgical transplantation and intranasal administration of MSCs in mouse models of glioblastoma and Alzheimer's disease respectively were performed. FINDINGS: Comparison of parental non-selected cells with isolated subpopulations revealed superior motility and migratory potential of sMSC and sNSC in vitro. We identified podoplanin as a major regulator of migratory features of sMSC/sNSC. Podoplanin engineering improved oncovirolytic activity of virus-loaded NSC on distantly located glioblastoma cells. Finally, sMSC displayed more targeted migration to the tumour site in a mouse glioblastoma model and remarkably higher potency to reduce pathological hallmarks and memory deficits in transgenic Alzheimer's disease mice. INTERPRETATION: Functional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy. FUNDING: This work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy.

BACKGROUND: Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. METHODS: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. FINDINGS: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. INTERPRETATION: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. FUNDING: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives.

Potential of gadolinium as contrast material in second generation dual energy computed tomography - An ex vivo phantom study.

PURPOSE: To evaluate the potential of gadolinium (Gd) as contrast material (CM) in second generation dual energy computed tomography (DECT). MATERIAL AND METHODS: In a phantom model, DECT post-processing was used to increase Gd attenuation using advanced monoenergetic extrapolation (MEI), to create virtual non-contrast images (Gd-VNC) and Gd maps and to quantify Gd content. Dilutions of Gd and iodinated CM (7-296 HU) were filled in syringes, placed in an attenuation phantom and scanned with standard DECT protocols (80 &100/Sn140 kV). MEI (40-190 keV) and VNC images as well as Gd maps were computed. The amount of Gd was quantified and the accuracy was compared to iodine images. Linear regression models were calculated to evaluate Gd attenuation of equivolume CM doses and clinical MRI doses. RESULTS: Applying monoenergetic reconstructions and using Gd as contrast agent (Gd MEI 40 keV) doubled Hounsfield-Units (HU) and 90% of the SNR (averaged: 225 HU, SNR3.1) are achievable, as compared to iodinated CM at 120 kV (averaged:110 HU, SNR3.5), at Gd doses of 1.0mmol/kg BW. The accuracies of Gd-VNC (deviation, 6±12 HU) images and Gd quantification (measurement error, 17%) were not significantly different to those of iodine enhanced images (VNC:deviation, 2±11 HU; measurement error,14%). CONCLUSION: Using monoenergetic extrapolation at 40keV, it is possible to increase Gd-CM attenuation significantly. Thus, equivalent HU and half the SNR in comparison to a standard dose of ICM at 120kV can be expected at a Gd-CM dose of 0.5mmol/kg BW. Post-processing features of iodine based DECT like monoenergetic or VNC images, iodine maps or quantification of CM are feasible with the use of Gd-CM.

International Clinical Protocol on Vestibular Disorders (Dizziness).

26-28 May at 43 Congress of Neurootological and Equilibriometric Society (Budapest, Hungary) International Clinical Protocol on Vestibular Disorders (Dizziness) being discussed and accepted as Consensus Document. Cochrane reports estimates that dizziness has prevalence of 22.9% in the last 12 months and an incidence of 3.1%. Only 1.8% of adults consulted a physician in the last 12 months. Cochrane reviews suggest that the evidence base for dizziness evaluation is weak, thus necessitates the creation of evidence-based document. Protocol is based at the new concept of vestibular system, which involves the vestibular peripheral sensors, space orientation tetrad, vestibular presentations in the brain cortex and vestibular effectory projections in the brain. Labyrinth consists of sensors, for which six modalities are adequate: 1. acceleration, 2. gravitation, 3. low frequency whole-body vibration, 4. Infrasound, 5. magnetic impulse, 6. metabolic changes. Vestibular system from rhomboid fosse gets the inputs from visual, acoustic, somatosensory organs, integrating them and forming space perception and orientation. Interaction with space is realized through sensory, motor, vegetative and limbic projections. So, vestibular disturbances may manifest as paropsia, tinnitus, numbness. Vestibular evoked potentials (not VEMP) and craniocorpography have highest sensitivity (90% and more). As vestibular dysfunction has recurrent character patients need monitoring.

Viability and MR detectability of iron labeled mesenchymal stem cells used for endoscopic injection into the porcine urethral sphincter.

Direct stem cell therapies for functionally impaired tissue require a sufficient number of cells in the target region and a method for verifying the fate of the cells in the subsequent time course. In vivo MRI of iron labeled mesenchymal stem cells has been suggested to comply with these requirements. The study was conducted to evaluate proliferation, migration, differentiation and adhesion effects as well as the obtained iron load of an iron labeling strategy for mesenchymal stem cells. After injection into the porcine urethral sphincter, the labeled cells were monitored for up to six months using MRI. Mesenchymal stem cells were labeled with ferucarbotran (60/100/200 µg/mL) and ferumoxide (200 µg/mL) for the analysis of migration and viability. Phantom MR measurements were made to evaluate effects of iron labeling. For short and long term studies, the iron labeled cells were injected into the porcine urethral sphincter and monitored by MRI. High resolution anatomical images of the porcine urethral sphincter were applied for detection of the iron particles with a turbo-spin-echo sequence and a gradient-echo sequence with multiple TE values. The MR images were then compared with histological staining. The analysis of cell function after iron labeling showed no effects on proliferation or differentiation of the cells. Although the adherence increases with higher iron dose, the ability to migrate decreases as a presumed effect of iron labeling. The iron labeled mesenchymal stem cells were detectable in vivo in MRI and histological staining even six months after injection. Labeling with iron particles and subsequent evaluation with highly resolved three dimensional data acquisition allows sensitive tracking of cells injected into the porcine urethral sphincter for several months without substantial biological effects on mesenchymal stem cells.

Dual-Source Dual-Energy CT Angiography of the Supra-Aortic Arteries with Tin Filter: Impact of Tube Voltage Selection.

RATIONALE AND OBJECTIVES: Automatic bone and plaque subtraction (BPS) in computed tomographic angiographic (CTA) examinations using dual-energy CT (DECT) remains challenging because of beam-hardening artifacts in the shoulder region and close proximity of the internal carotid artery to the base of the skull. The selection of the tube voltage combination in dual-source CT influences the spectral separation and the susceptibility for artifacts. The purpose of this study was to assess which tube voltage combination leads to an optimal image quality of head and neck DECT angiograms after bone subtraction. MATERIALS AND METHODS: Fifty-one patients received tin-filter-enhanced DECT angiograms of the supra-aortic arteries using two voltage protocols: 24 patients were studied using 80/Sn140 kV and 27 using a 100/Sn140 kV protocol, both protocols with an additional tin filter. A commercially available DE-CTA BPS algorithm was used. Artificial vessel erosions in BPS maximum intensity projections (four-level Likert scale with CTA source data as reference) and vessel signal-to-noise ratio (SNR) were assessed in the level of the shoulders and the base of the skull in each patient and compared. RESULTS: At the level of the shoulder, 100/Sn140 kV achieved higher SNR (23.4 ± 6.4 at 80/Sn140 kV vs. 35.1 ± 11.8 at 100/Sn140 kV; P < .0001) with less erosions (erosion score 3.9 ± 0.4 in 80/Sn140 kV vs. 2.1 ± 1.3 in 100/Sn140 kV; P < .0001) than 80/Sn140 kV. At the level of the skull base, erosion scores and objective image quality of arterial segments were comparable with both protocols (P = .14). CONCLUSIONS: The 100/Sn140 kV protocol achieved more favorable results for BPS of the supra-aortic arteries than the 80/Sn140 kV protocol.

Dual-energy CT: virtual calcium subtraction for assessment of bone marrow involvement of the spine in multiple myeloma.

OBJECTIVE. Dual-energy CT (DECT) enables subtraction of calcium, facilitating the visualization of bone marrow (BM) in the axial skeleton. The purpose of this study was to assess whether DECT BM images have the potential to improve the detection of multifocal and diffuse BM infiltration in multiple myeloma (MM) in comparison with regular CT with MRI as the reference standard. SUBJECTS AND METHODS. This study included 32 consecutive patients who had known MM or presented with monoclonal gammopathy of unknown significance and underwent DECT and MRI of the axial skeleton. The degrees (none, n = 14; moderate, n = 10; and high, n = 8) and patterns (diffuse, n = 10 or multifocal, n = 8) of infiltration were assessed on MR images. Attenuation in BM and CT images in known uninvolved and involved areas was measured. Cutoff values of attenuation in BM images for infiltration in lytic and nonlytic lesions were established by ROC analysis. At least 120 days later, sensitivity and specificity for reading CT images alone and when using additional BM images were evaluated. RESULTS. ROC analysis revealed larger AUC in BM images than in CT images; cutoff values for marrow invasion in BM images were 4 and -3 HU in lytic and nonlytic lesions, respectively. In the blinded reading session, BM images improved the sensitivity for the detection of diffuse infiltration from 0 to as much as 75% for cases with high-grade infiltration. In multifocal patterns, BM images did not significantly change the detection rate. CONCLUSION. BM images have the potential to improve the sensitivity for detection of diffuse BM involvement in comparison with regular CT.

Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial.

OBJECTIVES: The purpose of this study was to evaluate the 5-year follow-up (FU) data of the THUNDER (Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries). BACKGROUND: The THUNDER trial was the first study to investigate the treatment of femoropopliteal arteries with a paclitaxel-coated balloon (PCB). METHODS: In 154 patients, femoropopliteal arteries were treated with PCB, with angioplasty with paclitaxel in contrast medium, or no paclitaxel (control). The primary endpoint was 6-month late lumen loss (LLL). Secondary endpoints included freedom from target lesion revascularization (TLR), binary restenosis rate, and amputation. The 5-year FU compares outcomes in patients treated with PCB and control subjects. Additionally, LLL at 6 months and TLR up to 5-year FU were analyzed in terms of sex and lesion length. RESULTS: Over the 5-year period, the cumulative number of patients with TLR remained significantly lower in the PCB group (21%) than in the control group (56%, p = 0.0005). In the small group of patients with angiographic and duplex sonographic follow-up, PCB was associated with a lower rate of binary restenosis (17% vs. 54%; p = 0.04). No signs of aneurysm formation or constrictive fibrosis were detected. Whereas LLL at 6-month FU did not differ between men and women in the PCB group, the TLR rate was lower in men than in women at 5-year FU. A benefit of PCB treatment in terms of LLL and TLR was seen independent of lesion length. CONCLUSIONS: The reduced TLR rate following PCB treatment was maintained over the 5-year FU period. No signs of drug-related local vessel abnormalities were detected. (Thunder Trial-Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries [THUNDER]; NCT00156624).

Tendinopathy of the achilles tendon: volume assessed by automated contour detection in submillimeter isotropic 3-dimensional magnetic resonance imaging data sets recorded at a field strength of 3 T.

OBJECTIVE: This prospective study assesses volume changes of the Achilles tendon in case of chronic tendinopathy (TEN), using an automated contour detection algorithm in submillimeter isotropic 3-dimensional magnetic resonance imaging data sets, recorded at 3 T. METHODS: Forty-one subjects (median age, 40 years; range, 19-68 years) were included in this prospective study and underwent nonenhanced magnetic resonance imaging of both Achilles tendons at 3 T, deploying a T2-weighted 3-dimensional Fast-Spin-Echo sequence with submillimeter resolution of 0.8 mm. Of the 41 subjects, 13 were classified as patients with TEN and 28 were healthy volunteers and served as control group. Of the 13 patients, 10 had unilateral TEN and 3 had bilateral TEN. Achilles tendons were automatically segmented in the T2-weighted magnetic resonance data sets for the evaluation of the tendon volume (0-3 cm proximal to the cranial border of the calcaneal bone). The total volume (length, 3 cm) was divided in 3 subvolumes of 1 cm length, named volume (0-1 cm), volume (1-2 cm), and volume (2-3 cm). Minimum and maximum tendon cross-sectional area within the total volume was processed. A standardized pain questionnaire was obtained from all patients. RESULTS: The automated contour detection algorithm worked reliably in all cases. The TEN group showed a significantly increased tendon volume compared to the control group (mean volume, 2.94 vs 2.43 mm; P < 0.05). The difference was most obvious concerning volume (2-3 cm) (P < 0.0001). Evaluation of clinical severity revealed a moderate correlation between VISA-score and tendon volume (2-3 cm) as well as the maximum/minimum tendon area (ρ = -0.44, ρ = -0.48, and ρ = -0.41). In case of unilateral TEN, the symptomatic side showed an increased tendon volume (2-3 cm) and increased minimum area (P < 0.05). CONCLUSIONS: Tendon volume and size are adequate surrogate parameters to differentiate patients with chronic TEN from healthy subjects, and may discriminate symptomatic TEN from asymptomatic "silent" TEN in patients with unilateral symptoms.

Vacuum-assisted breast biopsy with 7-gauge, 8-gauge, 9-gauge, 10-gauge, and 11-gauge needles: how many specimens are necessary?

BACKGROUND: Published national and international guidelines and consensus meetings on the use of vacuum-assisted biopsy (VAB) give different recommendations regarding the required numbers of tissue specimens depending on needle size and imaging method. PURPOSE: To evaluate the weights of specimens obtained with different VAB needles to facilitate the translation of the required number of specimens between different breast biopsy systems and needle sizes, respectively. MATERIAL AND METHODS: Five different VAB systems and seven different needle sizes were used: Mammotome® (11-gauge (G), 8-G), Vacora® (10-G), ATEC Sapphire™ (9-G), 8-G Mammotome® Revolve™, and EnCor Enspire® (10-G, 7-G). We took 24 (11-G) or 20 (7-10-G) tissue cores from a turkey breast phantom. The mean weight of a single tissue core was calculated for each needle size. A matrix, which allows the translation of the required number of tissue cores for different needle sizes, was generated. Results were compared to the true cumulative tissue weights of consecutively harvested tissue cores. RESULTS: The mean tissue weights obtained with the 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G needles were 0.084 g / 0.142 g / 0.221 g / 0.121 g / 0.192 g / 0.334 g / 0.363 g, respectively. The calculated required numbers of VAB tissue cores for each needle size build the matrix. For example, the minimum calculated number of required cores according to the current German S3 guideline is 20 / 12 / 8 / 14 / 9 / 5 / 5 for needles of 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G size. These numbers agree with the true cumulative tissue weights. CONCLUSION: The presented matrix facilitates the translation of the required number of VAB specimens between different needle sizes and thereby eases the implementation of current guidelines and consensus recommendations into clinical practice.

Diffusion-weighted imaging during MR-guided radiofrequency ablation of hepatic malignancies: analysis of immediate pre- and post-ablative diffusion characteristics.

BACKGROUND: Previous studies have shown a benefit of magnetic resonance (MR)-diffusion-weighted imaging (DWI) for follow-up after liver radiofrequency (RF) ablation. However, no data are available concerning acute changes of DWI characteristics immediately after RF ablation. PURPOSE: To analyze and compare the MR-diffusion characteristics of pre-interventional hepatic malignancies and the ablation zone during successful MR-guided RF ablation. MATERIAL AND METHODS: This retrospective study was conducted in accordance with the guidelines of the local institutional review board. Forty-seven patients with 29 HCC (24 patients) and 30 hepatic metastases (23 patients) underwent MR-guided radiofrequency ablation including DWI before and immediately after ablation (b = 0, 400, 800 s/mm(2)). Two reviewers (A and B) analyzed DWI with focus on detectability of the tumor before ablation and characteristics of the coagulative area after treatment. Mean apparent diffusion coefficient (ADC) was compared between liver, untreated tumor, and hyperintense areas in post-ablative DWI (b = 800 s/mm(2)) with the paired Student's t-test. RESULTS: Pre-ablative: the reviewers classified 19/29 (A) and 23/29 (B) HCC and 25/30 (A and B) metastases as detectable in DWI. Post-ablative: a hyperintense rim surrounding the ablation zone was observed in 28/29 treated HCC and 30/30 treated metastases (A and B). A homogenous hypointense central ablation zone was found in 18/29 (A) and 20/29 (B) treated HCC and 17/30 (A & B) treated metastases in DWI. ADC of the rim was significantly lower than ADC of the liver (P < 0.001). CONCLUSION: DWI enables visualization of the target tumor in MR-guided liver radiofrequency ablation in most cases. A common post-ablative DWI finding is a hyperintense rim with decreased ADC surrounding the ablation zone.

Noise-optimized virtual monoenergetic images and iodine maps for the detection of venous thrombosis in second-generation dual-energy CT (DECT): an ex vivo phantom study.

AIMS AND OBJECTIVES: Deep venous thrombosis (DVT) can be difficult to detect using CT due to poor and heterogeneous contrast. Dual-energy CT (DECT) allows iodine contrast optimization using noise-optimized monoenergetic extrapolations (MEIs) and iodine maps (IMs). Our aim was to assess whether MEI and IM could improve the delineation of thrombotic material within iodine-enhanced blood compared to single-energy CT (SECT). MATERIALS AND METHODS: Six vessel phantoms, including human thrombus and contrast media-enhanced blood and one phantom without contrast, were placed in an attenuation phantom and scanned with DECT 100/140 kV and SECT 120 kV. IM, virtual non-contrast images (VNC), mixed images, and MEI were calculated. Attenuation of thrombi and blood were measured. Contrast and contrast-to-noise-ratios (CNRs) were calculated and compared among IM, VNC, mixed images, MEI, and SECT using paired t tests. RESULTS: MEI40keV and IM showed significantly higher contrast and CNR than SE120kV from high to intermediate iodine concentrations (contrast:pMEI40keV < 0.002,pIM < 0.005;CNR:pMEI40keV < 0.002,pIM < 0.004). At low iodine concentrations, MEI190keV and VNC images showed significantly higher contrast and CNR than SE120kV with inverted contrasts (contrast:pMEI190keV < 0.008,pVNC < 0.002;CNR:pMEI190keV < 0.003,pVNC < 0.002). CONCLUSIONS: Noise-optimized MEI and IM provide significantly higher contrast and CNR in the delineation of thrombosis compared to SECT, which may facilitate the detection of DVT in difficult cases. KEY POINTS: • Poor contrast makes it difficult to detect thrombosis in CT. • Dual-energy-CT allows contrast optimization using monoenergetic extrapolations (MEI) and iodine maps (IM). • Noise-optimized-MEI and IM are significantly superior to single-energy-CT in delineation of thrombosis. • Noise-optimized-MEI and IM may facilitate the detection of deep vein thrombosis.

Primary localization and tumor thickness as prognostic factors of survival in patients with mucosal melanoma.

BACKGROUND: Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations. METHODOLOGY: 116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages. PRINCIPAL FINDINGS: We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas. CONCLUSION: Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p < 0.0001).

Added value of integrated circuit detector in head CT: objective and subjective image quality in comparison to conventional detector design.

RATIONALE AND OBJECTIVES: A new computed tomography (CT) detector with integrated electric components and shorter conducting pathways has recently been introduced to decrease system inherent electronic noise. The purpose of this study was to assess the potential benefit of such integrated circuit detector (ICD) in head CT by comparing objective and subjective image quality in low-dose examinations with a conventional detector design. MATERIALS AND METHODS: Using a conventional detector, reduced-dose noncontrast head CT (255 mAs; effective dose, 1.7 mSv) was performed in 25 consecutive patients. Following transition to ICD, 25 consecutive patients were scanned using identical imaging parameters. Images in both groups were reconstructed with iterative reconstruction (IR) and filtered back projection (FBP) and assessed in terms of quantitative and qualitative image quality. RESULTS: Acquisition of head CT using ICD increased signal-to-noise ratio of gray and white matter by 14% (10.0 ± 1.6 vs. 11.4 ± 2.5; P = .02) and 17% (8.2 ± 0.8 vs. 9.6 ± 1.5; P = .000). The associated improvement in contrast-to-noise ratio was 12% (2.0 ± 0.5 vs. 2.2 ± 0.6; P = .121). In addition, there was a 51% increase in objective image sharpness (582 ± 85 vs. 884.5 ± 191; change in HU/Pixel; P < .000). Compared to standard acquisitions, subjective grading of noise and overall image quality scores were significantly improved with ICD (2.1 ± 0.3 vs. 1.6 ± 0.3; P < .000; 2.0 ± 0.5 vs. 1.6 ± 0.3; P = .001). Moreover, streak artifacts in the posterior fossa were substantially reduced (2.3 ± 0.7 vs. 1.7 ± 0.5; P = .004). CONCLUSIONS: At the same radiation level, acquisition of head CT with ICD achieves superior objective and subjective image quality and provides potential for significant dose reduction.

Transarterial chemoembolization using drug eluting beads and subsequent percutaneous MR-guided radiofrequency ablation in the therapy of intermediate sized hepatocellular carcinoma.

OBJECTIVE: To evaluate safety, efficacy, survival and recurrence-free survival of transarterial chemoembolization (TACE) with drug eluting (DC) beads combined with MR-guided radiofrequency (RF) ablation for the treatment of hepatocellular carcinomas (HCC) larger than 3 cm. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. 20 patients (69.6 years ± SD 8.8) with HCC underwent DC Bead TACE and subsequent MR-guided RF ablation. Treatment interval varied between 5 and 15 days. Mean HCC diameter was 39 mm ± SD 7 mm (range 31-50mm). Rates of recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: Technical success rate, primary and secondary technical effectiveness rate were 100%, 90% and 95%, respectively. Local tumour progression developed in one patient. Cumulative survival rates at 1, 3 and 5 years were 90% (Confidence Interval [CI]: 67%-97%), 50% (CI: 29%-70%), 27% (CI: 11%-51%) respectively. Median survival time was 37.4 months. During follow up (mean: 39.1 months ± SD 22.4; range 5-84 months), tumour progression in untreated liver developed in 14 cases. Cumulative recurrence-free survival rates at 1, 3 and 5 years were 48% (CI: 27-69%), 16% (5-39%), 16% (5-39%) respectively. Median recurrence-free survival time was 10.7 months. One major complication occurred due to misdiagnosed local recurrence. CONCLUSION: In conclusion, we demonstrated that MR-guided RF ablation with subsequent DC Bead TACE is safe and effective in local tumour control in patients with intermediate sized HCC.

Single-source dual-energy computed tomography: use of monoenergetic extrapolation for a reduction of metal artifacts.

OBJECTIVES: The objective of this study was to retrospectively determine the potential of virtual monoenergetic (ME) reconstructions for a reduction of metal artifacts using a new-generation single-source computed tomographic (CT) scanner. MATERIALS AND METHODS: The ethics committee of our institution approved this retrospective study with a waiver of the need for informed consent. A total of 50 consecutive patients (29 men and 21 women; mean [SD] age, 51.3 [16.7] years) with metal implants after osteosynthetic fracture treatment who had been examined using a single-source CT scanner (SOMATOM Definition Edge; Siemens Healthcare, Forchheim, Germany; consecutive dual-energy mode with 140 kV/80 kV) were selected. Using commercially available postprocessing software (syngo Dual Energy; Siemens AG), virtual ME data sets with extrapolated energy of 130 keV were generated (medium smooth convolution kernel D30) and compared with standard polyenergetic images reconstructed with a B30 (medium smooth) and a B70 (sharp) kernel. For quantification of the beam hardening artifacts, CT values were measured on circular lines surrounding bone and the osteosynthetic device, and frequency analyses of these values were performed using discrete Fourier transform. A high proportion of low frequencies to the spectrum indicates a high level of metal artifacts. The measurements in all data sets were compared using the Wilcoxon signed rank test. RESULTS: The virtual ME images with extrapolated energy of 130 keV showed significantly lower contribution of low frequencies after the Fourier transform compared with any polyenergetic data set reconstructed with D30, B70, and B30 kernels (P < 0.001). CONCLUSIONS: Sequential single-source dual-energy CT allows an efficient reduction of metal artifacts using high-energy ME extrapolation after osteosynthetic fracture treatment.

Simultaneous whole-body PET/MR imaging in comparison to PET/CT in pediatric oncology: initial results.

PURPOSE: To compare positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for lesion detection and interpretation, quantification of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake, and accuracy of MR-based PET attenuation correction in pediatric patients with solid tumors. Materials and Methods This prospective study had local ethics committee and German Federal Institute for Drugs and Medical Devices approval. Written informed consent was obtained from all patients and legal guardians. Twenty whole-body (18)F-FDG PET/CT and (18)F-FDG PET/MR examinations were performed in 18 pediatric patients (median age, 14 years; range, 11-17 years). (18)F-FDG PET/CT and (18)F-FDG PET/MR data were acquired sequentially on the same day for all patients. PET standardized uptake values (SUVs) were quantified with volume of interest measurements in lesions and healthy tissues. MR-based PET attenuation correction was compared with CT-derived attenuation maps (µ-maps). Lesion detection was assessed with separate reading of PET/CT and PET/MR data. Estimates of radiation dose were derived from the applied doses of (18)F-FDG and CT protocol parameters. Descriptive statistical analyses were performed to report correlation coefficients and relative deviations for comparison of SUVs, rates of lesion detection, and percentage reductions in radiation dose. RESULTS: PET SUVs showed strong correlations between PET of PET/CT (PETCT) and PET of PET/MR (PETMR) (r > 0.85 for most tissues). Apart from drawbacks of MR-based PET attenuation correction in osseous structures and lungs, similar SUVs were found on PET images corrected with CT-based µ-maps (13.1% deviation of SUVs for bone marrow and <5% deviation for other tissues). Lesion detection rate with PET/MR imaging was equivalent to that with PET/CT (61 areas of focal uptake on PETMR images vs 62 areas on PETCT images). Advantages of PET/MR were observed especially in soft-tissue regions. Furthermore, PET/MR offered significant dose reduction (73%) compared with PET/CT. CONCLUSION: Pediatric oncologic PET/MR is technically feasible, showing satisfactory performance for PET quantification with SUVs similar to those of PET/CT. Compared with PET/CT, PET/MR demonstrates equivalent lesion detection rates while offering markedly reduced radiation exposure. Thus, PET/MR is a promising modality for the clinical work-up of pediatric malignancies. Online supplemental material is available for this article.

Measurement of apparent diffusion coefficient with simultaneous MR/positron emission tomography in patients with peritoneal carcinomatosis: comparison with 18F-FDG-PET.

PURPOSE: To characterize peritoneal carcinomatosis (PC) of different histologically proven primary tumors based on diffusion-weighted imaging (DWI) and (18) F-FDG positron emission tomography (PET). MATERIALS AND METHODS: Forty-one patients underwent simultaneous MR/PET after clinically indicated (18) F-FDG-PET/CT. For all patients, histology of the primary tumor was obtained. MR protocol comprised anatomical imaging and axial DWI. Apparent diffusion coefficient (ADC) maps and FDG-PET were co-registered for evaluation of ADC and standard uptake value (SUV) of peritoneal lesions. Both lesion- and patient-based analysis was performed. Up to four peritoneal lesions were evaluated per patient. Mean and maximum standard uptake value (SUVmean , SUVmax ), mean and minimum ADC (ADCmean , ADCmin ) of each lesion were assessed. Spearman rank correlation (rs ) of ADC and SUV were calculated. SUV and ADC of ovarian and colorectal cancer lesions were compared using Wilcoxon test. RESULTS: Measurable lesions (n = 52) were found in 20 of 41 PC patients. Moderate, but significant correlation existed between ADC and SUV in the lesion-based as well as the patient-based analysis (lesion-based: SUVmean versus ADCmean rs = -0.58; SUVmax versus ADCmin rs = -0.56, all P < 0.0001; patient-based: SUVmean versus ADCmean rs = -0.64, P = 0.002; SUVmax versus ADCmin rs = -0.60, P = 0.005). ADC and SUV differed significantly between ovarian and colorectal cancer lesions (ADCmin : P < 0.0001; ADCmean : P < 0.0001; SUVmax : P = 0.002; SUVmean : P = 0.005). Overall, mucinous tumor entities showed a tendency to higher ADC and lower SUV. CONCLUSION: PC lesions showed significant differences in glucose uptake and diffusion characteristics depending on primary tumor histology. These differences should be considered when interpreting FDG-PET and DWI in PC patients.