Diffusion tensor imaging and tractography for preoperative assessment of benign peripheral nerve sheath tumors.

PURPOSE: To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors. METHOD: MR imaging at 3 T was performed in 22 patients (mean age 41.9 ±â€¯17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed. RESULTS: On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ±â€¯0.2 × 10-3 mm2/s) was significantly lower than in neurofibromas (1.8 ±â€¯0.2 × 10-3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10-3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69). CONCLUSIONS: Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.

3D grating-based X-ray phase-contrast computed tomography for high-resolution quantitative assessment of cartilage: An experimental feasibility study with 3T MRI, 7T MRI and biomechanical correlation.

OBJECTIVE: Aim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage. MATERIALS AND METHODS: In an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses. RESULTS: PCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses. CONCLUSION: In conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure.

Quantitative magnetic resonance imaging of the upper trapezius muscles - assessment of myofascial trigger points in patients with migraine.

BACKGROUND: Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. METHODS: Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. RESULTS: The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. CONCLUSIONS: Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Noninvasive quantitative assessment of microcirculatory disorders of the upper extremities with 2D fluorescence optical imaging.

BACKGROUND: Quantitative Imaging of microcirculatory disorders is challenging. OBJECTIVE: To investigate the feasibility of 2D Fluorescence Optical Imaging (FOI) for characterization and quantification of microcirculatory disorders in peripheral arterial occlusive disease (PAOD) of the upper extremity. METHODS: 9 patients with various clinical presentations of PAOD of the upper extremity were included. Quantitative analysis of both hands was performed by assessing the fluorescence intensity of Indocyanine Green (ICG) dynamically over a time period of 360 seconds. Analysis of the signal intensity within multiple regions of both hands was calculated and time-dependent perfusion curves for each region of interest were plotted over time. RESULTS: Compared to the healthy, vascular non-impaired segments, pathological segments with an impaired tissue perfusion were identified through a decreased rate of early tissue enhancement (p = 0.02) and increased signal intensity of the optical perfusion agent per second (p < 0.001). The affected segments showed a decreased maximum signal intensity and a prolonged interval to reach the maximum signal intensity (time to peak). CONCLUSION: 2D FOI allows quantitative assessment of the peripheral microcirculation in various vascular pathophysiologies and is able to detect the impaired tissue perfusion in patients with vascular disorders of the upper extremity.

Assessment of quantification accuracy and image quality of a full-body dual-layer spectral CT system.

The performance of a recently introduced spectral computed tomography system based on a dual-layer detector has been investigated. A semi-anthropomorphic abdomen phantom for CT performance evaluation was imaged on the dual-layer spectral CT at different radiation exposure levels (CTDIvol of 10 mGy, 20 mGy and 30 mGy). The phantom was equipped with specific low-contrast and tissue-equivalent inserts including water-, adipose-, muscle-, liver-, bone-like materials and a variation in iodine concentrations. Additionally, the phantom size was varied using different extension rings to simulate different patient sizes. Contrast-to-noise (CNR) ratio over the range of available virtual mono-energetic images (VMI) and the quantitative accuracy of VMI Hounsfield Units (HU), effective-Z maps and iodine concentrations have been evaluated. Central and peripheral locations in the field-of-view have been examined. For all evaluated imaging tasks the results are within the calculated theoretical range of the tissue-equivalent inserts. Especially at low energies, the CNR in VMIs could be boosted by up to 330% with respect to conventional images using iDose/spectral reconstructions at level 0. The mean bias found in effective-Z maps and iodine concentrations averaged over all exposure levels and phantom sizes was 1.9% (eff. Z) and 3.4% (iodine). Only small variations were observed with increasing phantom size (+3%) while the bias was nearly independent of the exposure level (±0.2%). Therefore, dual-layer detector based CT offers high quantitative accuracy of spectral images over the complete field-of-view without any compromise in radiation dose or diagnostic image quality.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

OBJECTIVE: Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. MATERIALS AND METHODS: Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. RESULTS: Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). CONCLUSION: In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. KEY POINTS: • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Co-clinical Assessment of Tumor Cellularity in Pancreatic Cancer.

Purpose: Tumor heterogeneity is a hallmark of pancreatic ductal adenocarcinoma (PDAC). It determines tumor biology including tumor cellularity (i.e., amount of neoplastic cells and arrangement into clusters), which is related to the proliferative capacity and differentiation and the degree of desmoplasia among others. Given the close relation of tumor differentiation with differences in progression and therapy response or, e.g., the recently reported protective role of tumor stroma, we aimed at the noninvasive detection of PDAC groups, relevant for future personalized approaches. We hypothesized that histologic differences in PDAC tissue composition are detectable by the noninvasive diffusion weighted- (DW-) MRI-derived apparent diffusion coefficient (ADC) parameter.Experimental design: PDAC cellularity was quantified histologically and correlated with the ADC parameter and survival in genetically engineered mouse models and human patients.Results: Histologic analysis showed an inverse relationship of tumor cellularity and stroma content. Low tumor cellularity correlated with a significantly prolonged mean survival time (PDAClow = 21.93 months vs. PDACmed = 12.7 months; log-rank P < 0.001; HR = 2.23; CI, 1.41-3.53). Multivariate analysis using the Cox regression method confirmed tumor cellularity as an independent prognostic marker (P = 0.034; HR = 1.73; CI, 1.04-2.89). Tumor cellularity showed a strong negative correlation with the ADC parameter in murine (r = -0.84; CI, -0.90- -0.75) and human (r = -0.79; CI, -0.90 to -0.56) PDAC and high preoperative ADC values correlated with prolonged survival (ADChigh = 41.7 months; ADClow = 14.77 months; log rank, P = 0.040) in PDAC patients.Conclusions: This study identifies high tumor cellularity as a negative prognostic factor in PDAC and supports the ADC parameter for the noninvasive identification of PDAC groups. Clin Cancer Res; 23(6); 1461-70. ©2016 AACR.

Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

PURPOSE: The aim of this study was to prospectively evaluate the value of [11C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. METHODS: Thirty-two patients were referred for [11C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [11C] Choline uptake (SUVmax, SUVmean), CT derived Houndsfield units (HUmax, HUmean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUVmax, SUVmean, HUmax, HUmean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUVmax and SUVmean (early and late) and changes of PSAearly and PSAlate were evaluated. Prognostic value of initial SUVmax and SUVmean was assessed. Statistical analyses were performed using SPSS. RESULTS: In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUVmax and SUVmean were statistically significantly higher in nPD (applying clinical criteria). CONCLUSION: There is no significant correlation between change in choline uptake in [11C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [11C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

A Monte Carlo software bench for simulation of spectral k-edge CT imaging: Initial results.

PURPOSE: Spectral Computed Tomography (SCT) systems equipped with photon counting detectors (PCD) are clinically desired, since such systems provide not only additional diagnostic information but also radiation dose reductions by a factor of two or more. The current unavailability of clinical PCDs makes a simulation of such systems necessary. METHODS: In this paper, we present a Monte Carlo-based simulation of a SCT equipped with a PCD. The aim of this development is to facilitate research on potential clinical applications. Our MC simulator takes into account scattering interactions within the scanned object and has the ability to simulate scans with and without scatter and a wide variety of imaging parameters. To demonstrate the usefulness of such a MC simulator for development of SCT applications, a phantom with contrast targets covering a wide range of clinically significant iodine concentrations is simulated. With those simulations the impact of scatter and exposure on image quality and material decomposition results is investigated. RESULTS: Our results illustrate that scatter radiation plays a significant role in visual as well as quantitative results. Scatter radiation can reduce the accuracy of contrast agent concentration by up to 15%. CONCLUSIONS: We present a reliable and robust software bench for simulation of SCTs equipped with PCDs.

In-vivo assessment of femoral bone strength using Finite Element Analysis (FEA) based on routine MDCT imaging: a preliminary study on patients with vertebral fractures.

PURPOSE: To experimentally validate a non-linear finite element analysis (FEA) modeling approach assessing in-vitro fracture risk at the proximal femur and to transfer the method to standard in-vivo multi-detector computed tomography (MDCT) data of the hip aiming to predict additional hip fracture risk in subjects with and without osteoporosis associated vertebral fractures using bone mineral density (BMD) measurements as gold standard. METHODS: One fresh-frozen human femur specimen was mechanically tested and fractured simulating stance and clinically relevant fall loading configurations to the hip. After experimental in-vitro validation, the FEA simulation protocol was transferred to standard contrast-enhanced in-vivo MDCT images to calculate individual hip fracture risk each for 4 subjects with and without a history of osteoporotic vertebral fractures matched by age and gender. In addition, FEA based risk factor calculations were compared to manual femoral BMD measurements of all subjects. RESULTS: In-vitro simulations showed good correlation with the experimentally measured strains both in stance (R2 = 0.963) and fall configuration (R2 = 0.976). The simulated maximum stress overestimated the experimental failure load (4743 N) by 14.7% (5440 N) while the simulated maximum strain overestimated by 4.7% (4968 N). The simulated failed elements coincided precisely with the experimentally determined fracture locations. BMD measurements in subjects with a history of osteoporotic vertebral fractures did not differ significantly from subjects without fragility fractures (femoral head: p = 0.989; femoral neck: p = 0.366), but showed higher FEA based risk factors for additional incident hip fractures (p = 0.028). CONCLUSION: FEA simulations were successfully validated by elastic and destructive in-vitro experiments. In the subsequent in-vivo analyses, MDCT based FEA based risk factor differences for additional hip fractures were not mirrored by according BMD measurements. Our data suggests, that MDCT derived FEA models may assess bone strength more accurately than BMD measurements alone, providing a valuable in-vivo fracture risk assessment tool.

Assessment of whole spine vertebral bone marrow fat using chemical shift-encoding based water-fat MRI.

BACKGROUND: The assessment of bone marrow composition has recently gained significant attention due to its association with bone loss pathophysiology and cancer therapy-induced bone marrow damage. The purpose of our study was to investigate the anatomical variation of the vertebral bone marrow fat using chemical shift-encoding based water-fat MRI and to assess the repeatability of these measurements. METHODS: Chemical shift-encoding based water-fat MRI of the whole spine was performed in 28 young, healthy subjects (17 males, 11 females, 26 ± 4 years). Six subjects were scanned three times with repositioning to assess the repeatability of these measurements. Proton density fat fraction (PDFF) maps were computed and manually segmented to obtain PDFF of C3-L5. RESULTS: Mean PDFF of all subjects significantly increased from C3 to L5 (P < 0.05) with r = 0.88 (P < 0.05). PDFF averaged over C3-7, T1-6, T7-12, and L1-5 of males and females amounted to 31.7 ± 7.9% and 23.0 ± 7.8% (P = 0.002), 33.8 ± 6.8% and 24.6 ± 8.8% (P = 0.005), 33.8 ± 6.4% and 26.1 ± 6.4% (P = 0.023), and 38.8 ± 7.6% and 31.5 ± 12.4% (P = 0.063), respectively. The repeatability for PDFF measurements expressed as absolute precision error was 1.7% averaged over C3-L5. CONCLUSION: Whole spine vertebral bone marrow fat could be reproducibly assessed by using chemical shift-encoding based water-fat MRI and showed anatomical variations.

Local Staging of Soft-Tissue Sarcoma: Emphasis on Assessment of Neurovascular Encasement-Value of MR Imaging in 174 Confirmed Cases.

PURPOSE: To evaluate utility of magnetic resonance (MR) imaging in local staging of soft-tissue sarcoma, with an emphasis on assessment of neurovascular encasement. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent requirement was waived. Preoperative MR images in 174 patients with soft-tissue sarcoma were analyzed by two readers. Tumor staging according to the American Joint Committee on Cancer/Union International Contre le Cancer and Enneking staging systems and analysis of osseous and articular invasion were performed. To assess neurovascular encasement, contact between tumor and arteries, between tumor and veins, and between tumor and nerves was classified (no contact, contact ≤90°, 91°-180°, 181°-270°, >271°). Interobserver agreement was determined; imaging findings were correlated with intraoperative findings and/or histopathologic findings (Pearson correlation coefficient [r] and Cohen κ coefficient). RESULTS: Intraoperative evaluation and/or histopathologic evaluation confirmed osseous, articular, and neurovascular invasion in 8.6%, 2.9%, and 25.3% of patients. Interobserver agreement was excellent for tumor staging (American Joint Committee on Cancer/Union International Contre le Cancer staging, κ = 0.811; Enneking staging, κ = 0.943) and osseous invasion (κ = 1.000). It was substantial for articular invasion (κ = 0.794). Sensitivity and specificity for osseous invasion were 100% and 98.7%, respectively (both readers). For articular invasion, sensitivity was 80% (both readers); specificities were 100% and 98.8% for readers 1 and 2, respectively. Interobserver agreement in quantifying contact between tumor and vessels and between tumor and nerves was excellent for arteries, veins, and nerves (κ = 0.845, 0.892, 0.893, respectively). Receiver operating characteristic analysis revealed optimal threshold of greater than 180° for prediction of arterial and venous encasement (both readers). For neural encasement, optimal threshold was greater than 180° (reader 1) and greater than 270° (reader 2). Sensitivities in diagnosing encasement for arteries, veins, and nerves were 84.6%, 84.6%, and 77.8% (reader 1) and 84.6%, 84.6%, and 72.2% (reader 2). Specificities for encasement of arteries, veins, and nerves, respectively, were 97.5%, 97.5%, and 93.2% (reader 1) and 93.8%, 94.7%, 97.3% (reader 2). CONCLUSION: MR imaging allows reliable and accurate local staging of soft-tissue sarcoma. Encasement of arteries, veins, and nerves should be diagnosed, if the contact between tumor and vascular or neural circumference exceeds 180°.

MR arthrography including abduction and external rotation images in the assessment of atraumatic multidirectional instability of the shoulder.

OBJECTIVE: To evaluate diagnostic signs and measurements in the assessment of capsular redundancy in atraumatic multidirectional instability (MDI) of the shoulder on MR arthrography (MR-A) including abduction/external rotation (ABER) images. METHODS: Twenty-one MR-A including ABER position of 20 patients with clinically diagnosed MDI and 17 patients without instability were assessed by three radiologists. On ABER images, presence of a layer of contrast between the humeral head (HH) and the anteroinferior glenohumeral ligament (AIGHL) (crescent sign) and a triangular-shaped space between the HH, AIGHL and glenoid (triangle sign) were evaluated; centring of the HH was measured. Anterosuperior herniation of the rotator interval (RI) capsule and glenoid version were determined on standard imaging planes. RESULTS: The crescent sign had a sensitivity of 57 %/62 %/48 % (observers 1/2/3) and specificity of 100 %/100 %/94 % in the diagnosis of MDI. The triangle sign had a sensitivity of 48 %/57 %/48 % and specificity of 94 %/94 %/100 %. The combination of both signs had a sensitivity of 86 %/90 %/81 % and specificity of 94 %/94 %/94 %. A positive triangle sign was significantly associated with decentring of the HH. Measurements of RI herniation, RI width and glenoid were not significantly different between both groups. CONCLUSIONS: Combined assessment of redundancy signs on ABER position MR-A allows for accurate differentiation between patients with atraumatic MDI and patients with clinically stable shoulders; measurements on standard imaging planes appear inappropriate. KEY POINTS: MR arthrography has the possibility to accurately identify patients with atraumatic MDI. Imaging of the shoulder in abduction and external rotation provides additive information. Capsular enlargement of the shoulder can be diagnosed on MR arthrography.

Assessment of myocardial infarction and postinfarction scar remodeling with an elastin-specific magnetic resonance agent.

BACKGROUND: To prospectively evaluate an elastin-specific MR contrast agent (ESMA) for in vivo targeting of elastic fibers in myocardial infarction (MI) and postinfarction scar remodeling. METHODS AND RESULTS: MI was induced in C57BL/6J mice (n=40) by permanent ligation of the left anterior descending coronary artery. MRI was performed at 7 and 21 days after MI. The merits of gadolinium-based ESMA (Gd-ESMA) were compared with gadopentetic acid (Gd-DTPA) for infarct size determination, contrast-to-noise ratio (CNR), and enhancement kinetics. Specific binding in vivo was evaluated by blocking the molecular target using nonparamagnetic lanthanum-ESMA. In vivo imaging results were confirmed by postmortem triphenyltetrazolium chloride staining, elastica van Gieson staining, and Western blotting. Delayed enhancement MRI revealed prolonged enhancement of Gd-ESMA in the postischemic scar compared with Gd-DTPA. Infarct size measurements showed good agreement between Gd-ESMA and Gd-DTPA and were confirmed by ex vivo triphenyltetrazolium chloride staining. Preinjection of the blocking lanthanum-ESMA resulted in significantly lower CNR of Gd-ESMA at the infarct site (P=0.0019). Although no significant differences in CNR were observed between delayed enhancement imaging and Gd-DTPA between days 7 and 21 (1.8± versus 3.8; P=ns), Gd-ESMA showed markedly higher CNR on day 21 after MI (14.1 versus 4.9; P=0.0032), which correlated with increased synthesis of tropoelastin detected by Western blot analysis and histology. Higher CNR values for Gd-ESMA further correlated with improved ejection fraction of the mice on day 21 after MI. CONCLUSIONS: Gd-ESMA enables targeting of elastin within the infarct scar in a mouse model of MI. The imaging properties of Gd-ESMA allow quantification of intrascar elastin content in vivo and thereby provide potential for noninvasive characterization of postinfarction scar remodeling.

Cardioprotective C-kit⁺ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice - in-vivo assessment with fluorescence molecular imaging.

Cardiomyocyte loss via apoptosis plays a crucial role in ventricular remodeling following myocardial infarction (MI). Cell-based therapy approaches using bone marrow derived c-kit⁺ pluripotent cells may attenuate apoptosis following ischemic injury. We therefore thought to examine the early course of apoptosis following myocardial infarction - in-vivo - and non-invasively determine the effect of c-kit⁺ bone marrow cells on post-MI remodeling. We studied apoptosis in wild-type Kit(+/+) , c-kit mutant Kit(W)/Kit(W-v) and Kit(W)/Kit(W-v) mice after cell therapy with bone-marrow derived c-kit⁺ cells after ischemia-reperfusion injury. Mice were followed by hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) at 6h, 24h and 7 days after ischemia-reperfusion injury using an Annexin V-based fluorescent nanosensor targeting phosphatidylserine. Kit(W)/Kit(W-v) mice showed increased and prolonged apoptosis compared to control Kit(+/+) mice while c-kit cell therapy was able to attenuate the altered apoptosis rates. Increased apoptosis was accompanied by severe decline in heart function, determined by cardiac Magnetic Resonance Imaging, and cell therapy was able to rescue the animals from deleterious heart failure. Post-mortem cryoslicing and immunohistochemistry localized the fluorescence signal of the Annexin V sensor within the infarcted myocardium. Flow cytometry of digested infarct specimens identified apoptotic cardiomyocytes as the major source for the in-vivo Annexin V signal. In-vivo molecular imaging using hybrid FMT-XCT reveals increased cardiomyocyte apoptosis in Kit(W)/Kit(W-v) mice and shows that c-kit⁺ cardioprotective cells are able to attenuate post-MI apoptosis and rescue mice from progressive heart failure.

Three-dimensional magnetic resonance imaging using single breath-hold k-t BLAST for assessment of global left ventricular functional parameters.

OBJECTIVES: To determine the accuracy of three-dimensional k-t broad-use linear acquisition speed-up technique (k-t BLAST) accelerated magnetic resonance imaging (MRI) for the assessment of left ventricular (LV) parameters compared to segmented multiple breath-hold cine imaging. METHODS: A multislice cine (steady state free precession [SSFP]) sequence was performed with complete ventricular coverage during multiple breath-holds (temporal resolution 47 ms, voxel size 1.25 × 1.25 × 8 mm(3)). In addition, two k-t BLAST sequences with complete coverage were acquired, KT1 (temporal resolution 57 ms, voxel size 1.25 × 1.25 × 4 mm(3)) and k-t2 (temporal resolution 57 ms, voxel size 1.25 × 1.25 × 8 mm(3)), during a single breath-hold. For comparison of SSFP and k-t BLAST, LV parameters were determined: ejection fraction (EF), end-diastolic volume, end-systolic volume, and LV mass. RESULTS: EF was underestimated by KT1 (47%) and KT2 (48%) compared to the SSFP sequence (53%). All parameters showed high correlation with the k-t BLAST sequences and the SSFP sequence (r = 0.88-0.98, P < .001). The mean relative difference for KT1/KT2 compared to the SSFP sequence was -0.11/-0.09 for the EF, -0.073/-0.086 for the EDV, 0.044/0.051 for the ESV, and 0.085/0.12 for the LV mass. CONCLUSIONS: The use of three-dimensional k-t BLAST enabled a determination of the LV parameters with high correlation compared to the SSFP sequence. EF was slightly underestimated, and LV mass was slightly overestimated.

Rapid assessment of liver volumetry by a novel automated segmentation algorithm.

OBJECTIVE: This study aimed to evaluate a novel segmentation software for automated liver volumetry and segmentation regarding segmentation speed and interobserver variability. METHODS: Computed tomographic scans of 20 patients without underlying liver disease and 10 patients with liver metastasis from colorectal cancer were analyzed by a novel segmentation software. Liver segmentation was performed after manual placement of specific landmarks into 9 segments according to the Couinaud model as well as into 4 segments, the latter being import for surgery planning. Time for segmentation was measured and the obtained segmental and total liver volumes between the different readers were compared calculating intraclass correlations (ICCs). Volumes of liver tumor burden were evaluated similarly. RESULTS: Liver segmentation could be performed rapidly 3 minutes or less. Comparison of total liver volumes revealed a perfect ICC of greater than 0.997. Segmental liver volumes within the 9-part segmentation provided fair to moderate correlation for the left lobe and good to excellent correlations for the right lobe. When applying a 4-part segmentation relevant to clinical practice, strong to perfect agreement was observed. Similarly tumor volumes showed perfect ICC (>0.998). CONCLUSIONS: Rapid determination of total and segmental liver volumes can be obtained using a novel segmentation software suitable for daily clinical practice.

Evaluation of phase-sensitive versus magnitude reconstructed inversion recovery imaging for the assessment of myocardial infarction in mice with a clinical magnetic resonance scanner.

PURPOSE: To evaluate phase-sensitive inversion-recovery (PSIR) imaging at 1.5 T in a mouse model of permanent coronary artery ligation as a potentially rapid and robust alternative for the accurate assessment of myocardial infarction (MI) by cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: PSIR late gadolinium enhancement (LGE) imaging was compared to conventional 2D segmented inversion-recovery imaging for the assessment of murine MI. RESULTS: PSIR images provided comparable contrast and kinetics of intravenously injected gadopentetate dimeglumine (Gd-DTPA). At the mid-ventricular level there was good agreement between conventional IR and PSIR for infarct size assessment. After intravenous injection a limited time window of ∼6 minutes is available for delayed enhancement imaging in mice. Whole-heart infarct imaging with 1 mm thick slices was only possible in this restricted time frame when the PSIR method is applied, avoiding the need for repetitively adapting the correct inversion time. Infarct size determined by PSIR MRI demonstrated good agreement with postmortem histology. Infarct size determined by PSIR LGE MRI inversely correlates with left-ventricular function on day 7 after MI. CONCLUSION: The PSIR technique provides stable and consistent contrast between hyperenhanced and remote myocardium independent of the selected inversion time (TI) and proved to be a robust, fast, and accurate tool for the assessment of MI in mice.

Workflow and scan protocol considerations for integrated whole-body PET/MRI in oncology.

Integrated PET/MRI systems open exciting possibilities for clinical and research applications. However, compared with PET/CT, PET/MRI is a complex technique resulting in new problems and challenges, especially regarding workflow, scan protocols, and data analysis. This complexity applies in particular to examinations in oncology with partial- or whole-body coverage extending over several bed positions. Unlike diagnostic PET/CT, for which the clinical CT protocols can largely be copied from stand-alone CT, the design of a diagnostic MRI protocol for partial- or whole-body coverage is more complex and has to be adapted to the special requirements of PET/MRI to be both time-efficient and comprehensive. Here, we describe basic considerations concerning workflow, imaging protocols, and image analysis for whole-body PET/MRI in oncology, based on our experience with the first integrated PET/MRI scanner. The aim is to fully and optimally make use of the combined PET/MRI measurements in oncology, including identifying and reducing image artifacts as well as optimizing workflow beyond the mere fusion of 2 image datasets.