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.

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.

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-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.

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.

A comparison of internally water-perfused and cryogenically cooled monopolar and bipolar radiofrequency applicators in ex vivo liver samples.

RATIONALE AND OBJECTIVES: To evaluate the ex vivo ablation zones created in hepatic tissue using monopolar and bipolar gas- and water-cooled radiofrequency (RF) applicators. MATERIALS AND METHODS: RF ablations were performed on ex vivo bovine liver tissue using closed circuit water-cooled and closed circuit cryogenically cooled (via CO2 enthalpy) 15-ga linear-needle applicators. Both monopolar and bipolar electrode applicators were used, with the electric current administered ranging in 50-mA increments from 1100 to 1300 mA for the monopolar case, and from 500 to 700 mA for the bipolar case. Total ablation time was 15 minutes. Six tissue samples were ablated per setting. The ablated volumes were assumed to have a three-dimensional ellipsoid shape, with one long major axis and two smaller minor axes. Gross histology was used to measure the dimensions of the ablated regions to quantify the ablated volume, the dimensions of the axis, and the ratio between the long axis and the smallest minor axis, which was termed the ellipticity index. RESULTS: The gas-cooled monopolar applicator achieved the largest short-axis ablation diameter (4.05 ± 0.4 cm), followed by the water-cooled monopolar applicator (3.18 ± 0.29 cm). With the bipolar applicator, the gas-cooled applicators also achieved larger short-axis ablation diameters (3.02 ± 0.15 cm) than the water-cooled applicators (2.72 ± 0.29 cm). The gas-cooled monopolar applicator also provided the largest ablation volume (42.7 ± 10.7 mL) and the most spherically shaped lesions (ellipticity index: 1.21 ± 0.10). Lesion size increased with injected current up to a threshold current of 1200/1250 mA (monopolar water-/gas-cooled) and 600/650 mA (bipolar water-/gas-cooled), but dropped at greater values. CONCLUSIONS: Gas-cooled monopolar applicators were superior to the other tested applicators in terms of both volume and sphericity of the ablation zone.

Liver lesion conspicuity during real-time MR-guided radiofrequency applicator placement using spoiled gradient echo and balanced steady-state free precession imaging.

PURPOSE: To retrospectively evaluate the conspicuity of liver lesions in a fluoroscopic spoiled gradient echo (GRE) and a balanced steady-state free precession (SSFP) magnetic resonance imaging (MRI) sequence. MATERIALS AND METHODS: In all, 103 patients with hepatocellular carcinomas (HCC) (41) or liver metastases (67) were treated using MR-guided radiofrequency ablation in a wide-bore 1.5 T scanner. A multislice real-time spoiled GRE sequence allowing for a T1 weighting (T1W) and a balanced SSFP sequence allowing for a T2/T1W contrast were used for MR guidance. The contrast-to-noise-ratio (CNR) of the lesions was calculated and lesion conspicuity was assessed retrospectively (easily detectable / difficult to detect / not detectable). RESULTS: HCC was easily detectable in 33/52% (GRE/SSFP), difficult to detect in 30/18%, and not detectable in 37/30% of the cases. Mean CNR varied widely (9.1 for GRE vs. 16.4 for SSFP). Liver metastases were easily detectable in 58/41% (GRE/SSFP), difficult to detect in 14/21%, and not detectable in 28/38% of the cases. Mean CNR for liver metastases was 11.5 (GRE) vs. 12.7 (SSFP). Twenty percent of all lesions could not be detected with either of the MR fluoroscopy sequences. CONCLUSION: MR fluoroscopy using GRE and SSFP contrast enabled real-time detectability of 80% of the liver lesions.

Image-guided radiofrequency ablation of hepatocellular carcinoma (HCC): is MR guidance more effective than CT guidance?

OBJECTIVES: The purpose of the study was to retrospectively compare technique effectiveness of computed tomography (CT)-guided versus magnetic resonance (MR)-guided radiofrequency (RF) ablation of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In 35 consecutive patients 53 CT-guided (n=29) or MR-guided (n=24) ablation procedures were performed in the treatment of 56 (CT: 29; MR: 27) HCC. The entire ablation procedure was performed at a multislice CT-scanner or an interventional 0.2-Tesla MR-scanner. Assessment of treatment response was based on dynamic MR imaging at 1.5Tesla. The mean follow-up was 22.9 months. Primary technique effectiveness was assessed 4 months after ablation therapy. Secondary technique effectiveness was assessed 4 months after a facultative second ablation procedure. Primary and secondary technique effectiveness of CT-guided and MR-guided RF ablation was compared by using Chi-Square (likelihood ratio) test. RESULTS: Primary technique effectiveness after a single session was achieved in 26/27 (96.3%) HCC after MR-guided RF ablation and 23/29 (79.3%) HCC after CT-guided RF ablation (Chi-Square: p=0.04). Secondary technique effectiveness was achieved in 26/27 (96.3%) HCC after MR-guided RF ablation and in 26/29 (89.7%) HCC after CT-guided RF ablation (Chi-Square: p=0.32). A local tumor progression was detected in 8/52 (15.4%) tumors after initial technique effectiveness. Major complications were detected after 3/53 (5.7%) ablation procedures. CONCLUSIONS: CT-guided and MR-guided RF ablations are locally effective therapies in the treatment of HCC. Due to a higher rate of primary technique effectiveness MR-guided RF ablation may reduce the number of required sessions for complete tumor treatment.

BI-RADS® 3 lesions at contrast-enhanced breast MRI: is an initial short-interval follow-up necessary?

BACKGROUND: Magnetic resonance imaging (MRI) BI-RADS® 3 lesions should have a very high probability of being benign. To prove benignity most institutions do follow-up MRI. PURPOSE: To evaluate the necessity of initial short-interval follow-up after 6 months as it is suggested for mammographic BI-RADS®3 lesions. MATERIAL AND METHODS: We analyzed 163 consecutive MRI-BI-RADS® 3 lesions on follow-up MRI: 75 masses (46%), 67 foci (41.1%), and 21 (12.9%) non-mass-like enhancing lesions (NMLE). RESULTS: During MRI follow-up (mean time, 563 days) 20% of the lesions disappeared, 23% decreased, 52% did not change, and 4.9% showed increase. All increasing lesions were biopsied (5 benign, 2 ductal carcinoma in situ, 1 invasive carcinoma). The rate of malignancy was 1.8%. All malignant lesions (1 mass, 1 focus, 1 NMLE) showed increase at initial follow-up after a mean interval of 190 days. CONCLUSION: In this study the malignancy rate of MRI-BI-RADS® 3 lesions corresponded to mammographic BI-RADS® 3 lesions. Initial short-interval MRI should be suggested to identify malignant MRI-BI-RADS® 3 lesions.

Short-term exercise-induced changes in hydration state of healthy Achilles tendons can be visualized by effects of off-resonant radiofrequency saturation in a three-dimensional ultrashort echo time MRI sequence applied at 3 Tesla.

PURPOSE: Off-resonant RF saturation influences signal intensity dependent on free and bound water fractions as well as the macromolecular content. The extent of interaction between these compartments can be evaluated by using the off-resonance saturation ratio (OSR). Combined with UTE sequences quantification of OSR even in tendinous tissues with extremely fast signal decay is possible. The aim of this prospective study was to investigate short-term exercise-induced effects of hydration state of the Achilles tendon by means of OSR and tendon volume. MATERIALS AND METHODS: Measurements of OSR and tendon volume before and after ankle-straining activity were performed in seven healthy male volunteers (median age 29 years) using a 3D UTE sequence with implemented off-resonance saturation pulse at 3T (off-resonance frequency 2/3 kHz) and by an automated contour detection in isotropic T2-weighted MR images with sub-millimeter resolution, respectively. Different tendon regions were evaluated. Reproducibility of OSR was measured in subsequent imaging sets. Root-mean-square-deviation (RMSD) and coefficient of variations (CV) were determined. RESULTS: RMSD of OSR in resting position were between 0.006 and 0.01 for different tendon regions and off-resonance frequencies (CV 2 to 3%). A significant increase (P < 0.05) of OSR after exercise was seen in all tendon regions except at the insertion (off-resonance frequency 3 kHz). Tendon volume was decreased significantly after ankle-straining activity (P = 0.003). CONCLUSION: The observed decreased tendon volume and increased OSR directly after exercise indicates a short-term change in tendinous proton compartments, most likely a loss of free water molecules within the tendon.

Quick water-selective excitation of fast relaxing tissues with 3D UTE sequences.

PURPOSE: The aim of this study was to implement a time effective 1-1 double pulse water-selective excitation (WE) into a three-dimensional ultrashort echo time (UTE) sequence (WE-UTE) for visualization of short-T2 tissues with positive contrast and sufficient suppression of surrounding fat. METHODS: First, an analytical description of magnetization components in the steady state applying WE-UTE was derived and results were compared with numerical simulations based on Bloch's equations. Parameters were optimized for best positive contrast between short-T2 tissues and fat under consideration of variable relaxation properties over a broad range. Maximal signal yield and signal efficiency of on-resonant protons were compared with UTE sequences with and without off-resonance fat saturation (FatSat). WE-UTE was exemplarily applied for in-vivo musculoskeletal imaging on a 3T whole-body MR unit. RESULTS: Steady state magnetization of WE-UTE could be described analytically and showed excellent accordance with numerical simulations. Even for tissues with T2 = 1 ms WE-UTE resulted in 79% of maximal signal yield of UTE without FatSat and was more efficient regarding signal yield if compared with UTE with FatSat. Using WE-UTE in-vivo tendons and ligaments could be well delineated with positive contrast to surrounding fat. CONCLUSION: WE-UTE provides a quick method for visualizing short-T2 tissues with positive contrast.