Relaxation Along a Fictitious Field, continuous wave T1rho, adiabatic T1rho and adiabatic T2rho imaging of human gliomas at 3T: A feasibility study.

In pre-clinical models of brain gliomas, Relaxation Along a Fictitious Field in second rotating frame (TRAFF2), continues wave T1rho (T1ρcw), adiabatic T1rho (T1ρadiab), and adiabatic T2rho (T2ρadiab) relaxation time mappings have demonstrated potential to non-invasively characterize brain gliomas. Our aim was to evaluate the feasibility and potential of 4 different spin lock methods at 3T to characterize primary brain glioma. 22 patients (26-72 years) with suspected primary glioma. T1ρcw was performed using pulse peak amplitude of 500Hz and pulse train durations of 40 and 80 ms while the corresponding values for T1ρadiab, T2ρadiab, TRAFF2 were 500/500/500Hz and 48 and 96, 64 and 112, 45 and 90 ms, respectively. The parametric maps were calculated using a monoexponential model. Molecular profiles were evaluated from tissue specimens obtained during the resection. The lesion regions-of-interest were segmented from high intensity FLAIR using automatic segmentation with manual refinement. Statistical descriptors from the voxel intensity values inside each lesion and radiomic features (Pyrad MRC package) were calculated. From extracted radiomics, mRMRe R package version 2.1.0 was used to select 3 features in each modality for statistical comparisons. Of the 22 patients, 10 were found to have IDH-mutant gliomas and of those 5 patients had 1p/19q codeletion group comparisons. Following correction for effects of age and gender, at least one statistical descriptor was able to differentiate between IDH and 1p/19q codeletion status for all the parametric maps. In the radiomic analysis, corner-edge detector features with Harris-Stephens filtered signal showed significant group differences in IDH and 1p/19q codeletion groups. Spin lock imaging at 3T of human glioma was feasible and various qualitative parameters derived from the parametric maps were found to have potential to differentiate IDH and 1p19q codeletion status. Future larger prospective clinical trials are warranted to evaluate these methods further.

Observing the fragmentation of two expanding bullet types and a full metal-jacketed bullet with computed tomography-a forensic ballistics case study.

Computed tomography (CT) may have a crucial role in the forensic documentation and analysis of firearm injuries. The aim of this forensic ballistics case study was to explore whether two types of expanding bullets and a full metal-jacketed bullet could be differentiated by inspecting bullet fragments and fragmentation pattern in CT. Three types of .30 caliber bullets (full metal-jacketed Norma Jaktmatch, expanding full-copper Norma Ecostrike, and expanding soft-point Norma Oryx) were test fired from a distance of 5 m to blocks of 10% ballistic gelatine. CT scans of the blocks were obtained with clinical equipment and metal artifact reduction. Radiopaque fragments were identified and fragmentation parameters were obtained from the scans (total number of fragments, maximum diameter of the largest fragment, distance between entrance and the closest fragment, length of the fragment cloud, and maximum diameters of the fragment cloud). The fragmentation patterns were additionally visualized by means of 3D reconstruction. In CT, the bullet types differed in several fragmentation parameters. While the expanding full-copper bullet Ecostrike left behind only a single fragment near the end of the bullet channel, the soft-point Oryx had hundreds of fragments deposited throughout the channel. For both expanding bullets Ecostrike and Oryx, the fragments were clearly smaller than those left behind by the full metal-jacketed Jaktmatch. This was surprising as the full metal-jacketed bullet was expected to remain intact. The fragment cloud of Jaktmatch had similar mediolateral and superoinferior diameters to that of Oryx; however, fragments were deposited in the second half of the gelatine block, and not throughout the block. This case study provides a basis and potential methodology for further experiments. The findings are expected to benefit forensic practitioners with limited background information on gunshot injury cases, for example, those that involve several potential firearms or atypical gunshot wounds. The findings may prove beneficial for both human and wildlife forensics.

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer.

OBJECTIVES: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. METHODS: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. RESULTS: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. CONCLUSION: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. CLINICAL RELEVANCE STATEMENT: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. KEY POINTS: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI.

SPICY: a method for single scan rotating frame relaxometry.

T 1ρ is an NMR relaxation mode that is sensitive to low frequency molecular motions, making it an especially valuable tool in biomolecular research. Here, we introduce a new method, SPICY, for measuring T1ρ relaxation times. In contrast to conventional T1ρ experiments, in which the sequence is repeated many times to determine the T1ρ time, the SPICY sequence allows determination of T1ρ within a single scan, shortening the experiment time remarkably. We demonstrate the method using 1H T1ρ relaxation dispersion experiments. Additionally, we combine the sequence with spatial encoding to produce 1D images in a single scan. We show that T1ρ relaxation times obtained using the single scan approach are in good agreement with those obtained using the traditional experiments.

Lymphatic insufficiency leads to distinct myocardial infarct content assessed by magnetic resonance TRAFFn, T1ρ and T2 relaxation times.

The role of cardiac lymphatics in the pathogenesis of myocardial infarction (MI) is unclear. Lymphatic system regulates cardiac physiological processes such as edema and tissue fluid balance, which affect MI pathogenesis. Recently, MI and fibrosis have been assessed using endogenous contrast in magnetic resonance imaging (MRI) based on the relaxation along a fictitious field with rank n (RAFFn). We extended the RAFFn applications to evaluate the effects of lymphatic insufficiency on MI with comparison to longitudinal rotating frame (T1ρ) and T2 relaxation times. MI was induced in transgenic (TG) mice expressing soluble decoy VEGF receptor 3 that reduces lymphatic vessel formation and their wild-type (WT) control littermates for comparison. The RAFFn relaxation times with rank 2 (TRAFF2), and rank 4 (TRAFF4), T1ρ and T2 were acquired at time points 0, 3, 7, 21 and 42 days after the MI at 9.4 T. Infarct sizes were determined based on TRAFF2, TRAFF4, T1ρ and T2 relaxation time maps. The area of differences (AOD) was calculated based on the MI areas determined on T2 and TRAFF2, TRAFF4 or T1ρ relaxation time maps. Hematoxylin-eosin and Sirius red stained histology sections were prepared to confirm MI locations and sizes. MI was detected as increased TRAFF2, TRAFF4, T1ρ and T2 relaxation times. Infarct sizes were similar on all relaxation time maps during the experimental period. Significantly larger AOD values were found together with increased AOD values in the TG group compared to the WT group. Histology confirmed these findings. The lymphatic deficiency was found to increase cardiac edema in MI. The combination of TRAFF2 (or TRAFF4) and T2 characterizes MI and edema in the myocardium in both lymphatic insufficiency and normal mice without any contrast agents.

Machine Learning Prediction of Collagen Fiber Orientation and Proteoglycan Content From Multiparametric Quantitative MRI in Articular Cartilage.

BACKGROUND: Machine learning models trained with multiparametric quantitative MRIs (qMRIs) have the potential to provide valuable information about the structural composition of articular cartilage. PURPOSE: To study the performance and feasibility of machine learning models combined with qMRIs for noninvasive assessment of collagen fiber orientation and proteoglycan content. STUDY TYPE: Retrospective, animal model. ANIMAL MODEL: An open-source single slice MRI dataset obtained from 20 samples of 10 Shetland ponies (seven with surgically induced cartilage lesions followed by treatment and three healthy controls) yielded to 1600 data points, including 10% for test and 90% for train validation. FIELD STRENGTH/SEQUENCE: A 9.4 T MRI scanner/qMRI sequences: T1 , T2 , adiabatic T1ρ and T2ρ , continuous-wave T1ρ and relaxation along a fictitious field (TRAFF ) maps. ASSESSMENT: Five machine learning regression models were developed: random forest (RF), support vector regression (SVR), gradient boosting (GB), multilayer perceptron (MLP), and Gaussian process regression (GPR). A nested cross-validation was used for performance evaluation. For reference, proteoglycan content and collagen fiber orientation were determined by quantitative histology from digital densitometry (DD) and polarized light microscopy (PLM), respectively. STATISTICAL TESTS: Normality was tested using Shapiro-Wilk test, and association between predicted and measured values was evaluated using Spearman's Rho test. A P-value of 0.05 was considered as the limit of statistical significance. RESULTS: Four out of the five models (RF, GB, MLP, and GPR) yielded high accuracy (R2  = 0.68-0.75 for PLM and 0.62-0.66 for DD), and strong significant correlations between the reference measurements and predicted cartilage matrix properties (Spearman's Rho = 0.72-0.88 for PLM and 0.61-0.83 for DD). GPR algorithm had the highest accuracy (R2  = 0.75 and 0.66) and lowest prediction-error (root mean squared [RMSE] = 1.34 and 2.55) for PLM and DD, respectively. DATA CONCLUSION: Multiparametric qMRIs in combination with regression models can determine cartilage compositional and structural features, with higher accuracy for collagen fiber orientation than proteoglycan content. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

New methods for robust continuous wave T1ρ relaxation preparation.

Measurement of the longitudinal relaxation time in the rotating frame of reference (T1ρ ) is sensitive to the fidelity of the main imaging magnetic field (B0 ) and that of the RF pulse (B1 ). The purpose of this study was to introduce methods for producing continuous wave (CW) T1ρ contrast with improved robustness against field inhomogeneities and to compare the sensitivities of several existing and the novel T1ρ contrast generation methods with the B0 and B1 field inhomogeneities. Four hard-pulse and four adiabatic CW-T1ρ magnetization preparations were investigated. Bloch simulations and experimental measurements at different spin-lock amplitudes under ideal and non-ideal conditions, as well as theoretical analysis of the hard-pulse preparations, were conducted to assess the sensitivity of the methods to field inhomogeneities, at low (ω1 << ΔB0 ) and high (ω1 >> ΔB0 ) spin-locking field strengths. In simulations, previously reported single-refocus and new triple-refocus hard-pulse and double-refocus adiabatic preparation schemes were found to be the most robust. The mean normalized absolute deviation between the experimentally measured relaxation times under ideal and non-ideal conditions was found to be smallest for the refocused preparation schemes and broadly in agreement with the sensitivities observed in simulations. Experimentally, all refocused preparations performed better than those that were non-refocused. The findings promote the use of the previously reported hard-pulse single-refocus ΔB0 and B1 insensitive T1ρ as a robust method with minimal RF energy deposition. The double-refocus adiabatic B1 insensitive rotation-4 CW-T1ρ preparation offers further improved insensitivity to field variations, but because of the extra RF deposition, may be preferred for ex vivo applications.

AAV8-mediated sVEGFR2 and sVEGFR3 gene therapy combined with chemotherapy reduces the growth and microvasculature of human ovarian cancer and prolongs the survival in mice.

Background: Vascular endothelial growth factors (VEGFs) are major regulators of intratumoral angiogenesis in ovarian cancer (OVCA). Overexpression of VEGFs is associated with increased tumor growth and metastatic tendency and VEGF-targeting therapies are thus considered as potential treatments for OVCA. Here, we examined the antiangiogenic and antitumoral effects on OVCA of adeno-associated virus 8 (AAV8)-mediated expression of soluble VEGF receptors (sVEGFRs) sVEGFR2 and sVEGFR3 together with paclitaxel and carboplatin chemotherapy. Materials and methods: Immunodeficient mice were inoculated with human OVCA cell line SKOV-3m. Development of tumors was confirmed with magnetic resonance imaging (MRI) and mice were treated with gene therapy and paclitaxel and carboplatin chemotherapy. The study groups included (I) non-treated control group, (II) blank control vector AAV8-CMV, (III) AAV8-CMV with chemotherapy, (IV) AAV8-sVEGFR2, (V) AAV8-sVEGFR3, (VI) AAV8-sVEGFR2 and AAV8-sVEGFR3, and (VII) AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy. Antiangiogenic and antitumoral effects were evaluated with immunohistochemical stainings and serial MRI. Results: Reduced intratumoral angiogenesis was observed in all antiangiogenic gene therapy groups. The combined use of AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy suppressed ascites fluid formation and tumor growth, thus improving the overall survival of mice. Antitumoral effect was mainly caused by AAV8-sVEGFR2 while the benefits of AAV8-sVEGFR3 and chemotherapy were less prominent. Conclusion: Combined use of the AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy reduces intratumoral angiogenesis and tumor growth in OVCA mouse model. Results provide preclinical proof-of-concept for the use of soluble decoy VEGFRs and especially the AAV8-sVEGFR2 in the treatment of OVCA.

Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA. Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples. Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs. Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

Myocardium Assessment by Relaxation along Fictitious Field, Extracellular Volume, Feature Tracking, and Myocardial Strain in Hypertensive Patients with Left Ventricular Hypertrophy.

Background: Previous research has shown impaired global longitudinal strain (GLS) and slightly elevated extracellular volume fraction (ECV) in hypertensive patients with left ventricular hypertrophy (HTN LVH). Up to now, only little attention has been paid to interactions between macromolecules and free water in hypertrophied myocardium. Purpose: To evaluate the feasibility of relaxation along a fictitious field with rank 2 (RAFF2) in HTN LVH patients. Study Type. Single institutional case control. Subjects: 9 HTN LVH (age, 69 ± 10 years) and 11 control subjects (age, 54 ± 12 years). Field Strength/Sequence. Relaxation time mapping (T 1, T 1ρ , and T RAFF2 with 11.8 µT maximum radio frequency field amplitude) was performed at 1.5 T using a Siemens Aera (Erlangen, Germany) scanner equipped with an 18-channel body array coil. Assessment. ECV was calculated using pre- and postcontrast T 1, and global strains parameters were assessed by Segment CMR (Medviso AB Co, Sweden). The parametric maps of T 1ρ and T RAFF2 were computed using a monoexponential model, while the Bloch-McConnell equations were solved numerically to model effect of the chemical exchange during radio frequency pulses. Statistical Tests. Parametric maps were averaged over myocardium for each subject to be used in statistical analysis. Kolmogorov-Smirnov was used as the normality test followed by Student's t-test and Pearson's correlation to determine the difference between the HTN LVH patients and controls along with Hedges' g effect size and the association between variables, respectively. Results: T RAFF2 decreased statistically (83 ± 2 ms vs 88 ± 6 ms, P < 0.031), and global longitudinal strain was impaired (GLS, -14 ± 3 vs - 18 ± 2, P < 0.002) in HTN LVH patients compared to the controls, respectively. Also, significant negative correlation was found between T RAFF2 and GLS (r = -0.53, P < 0.05). Data Conclusion. Our results suggest that T RAFF2 decrease in HTN LVH patients may be explained by gradual collagen accumulation which can be reflected in GLS changes. Most likely, it increases the water proton interactions and consequently decreases T RAFF2 before myocardial scarring.

Relaxation anisotropy of quantitative MRI parameters in biological tissues.

Quantitative MR relaxation parameters vary in the sensitivity to the orientation of the tissue in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in various tissues. Ex vivo samples of each tissue type were prepared either from bovine knee (tendon, cartilage) or mouse (brain, spinal cord, heart, kidney), and imaged at 9.4 T MRI with T1, T2, continuous wave (CW-) T1ρ, adiabatic T1ρ and T2ρ, and Relaxation along fictitious field (RAFF2-4) sequences at five different orientations with respect to the main magnetic field. Relaxation anisotropy of the measured parameters was quantified and compared. The highly ordered collagenous tissues, i.e. cartilage and tendon, presented the highest relaxation anisotropy for T2, CW-T1ρ with spin-lock power < 1 kHz, Ad-T2ρ and RAFF2-4. Maximally anisotropy was 75% in cartilage and 30% in tendon. T1 and adiabatic T1ρ did not exhibit observable anisotropy. In the other measured tissue types, anisotropy was overall less than 10% for all the parameters. The results confirm that highly ordered collagenous tissues have properties that induce very clearly observable relaxation anisotropy, whereas in other tissues the effect is not as prominent. Quantitative comparison of anisotropy of different relaxation parameters highlights the importance of sequence choice and design in MR imaging.

A dose-neutral image quality comparison of different CBCT and CT systems using paranasal sinus imaging protocols and phantoms.

PURPOSE: To compare the image quality produced by equivalent low-dose and default sinus imaging protocols of a conventional dental cone-beam computed tomography (CBCT) scanner, an extremity CBCT scanner and a clinical multidetector computed tomography (MDCT) scanner. METHODS: Three different phantoms were scanned using dose-neutral ultra-low-dose and low-dose sinus imaging protocols, as well as default sinus protocols of each device. Quantified parameters of image quality included modulation transfer function (MTF) to characterize the spatial response of the imaging system, contrast-to-noise ratio, low contrast visibility, image uniformity and Hounsfield unit accuracy. MTF was calculated using the line spread and edge spread functions (LSF and ESF). RESULTS: The dental CBCT had superior performance over the extremity CBCT in each studied parameter at similar dose levels. The MDCT had better contrast-to-noise ratio, low contrast visibility and image uniformity than the CBCT scanners. However, the CBCT scanners had better resolution compared to the MDCT. Accuracy of HU values for different materials was on the same level between the dental CBCT and MDCT, but substantially poorer performance was observed with the extremity CBCT. CONCLUSIONS: The studied dental CBCT scanner showed superior performance over the studied extremity CBCT scanner when using dose-neutral imaging protocols. In case a dental CBCT is not available, the given extremity CBCT is still a viable option as it provides the benefit of high resolution over a conventional MDCT.

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position.

BACKGROUND: The heart's position determined as the heart-aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. PURPOSE: To investigate whether VAT and aortic length influence the HAA. MATERIAL AND METHODS: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. RESULTS: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°-130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°-124.7°) in patients with excessive VAT (P < 0.001). CONCLUSION: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Flow displacement and decreased wall shear stress might be associated with the growth rate of an ascending aortic dilatation.

OBJECTIVES: Our goal was to evaluate whether four-dimensional (4D) flow magnetic resonance imaging (MRI) can predict the growth rate of dilatation of the ascending aorta (AA) in patients with a tricuspid, normally functioning aortic valve. METHODS: In this prospective clinical study, aortic 4D flow MRI was performed at the Kuopio University Hospital on 30 patients diagnosed with AA dilatation (maximum diameter >40 mm) between August 2017 and July 2020. The MRI was repeated after a 1-year follow-up, with AA dimensions and 4D flow parameters analysed retrospectively at both time points. The standard error of measurement was used to assess the statistical significance of the growth rate of AA dilatation. Flow displacement (FD) was transformed to a class-scaled parameter using FD ≥5% as a threshold. RESULTS: Statistically significant growth [median 2.1 mm (1.5-2.2 mm); P = 0.03] was detected in 6 male patients (20%); the AA diameter remained unchanged [0.2 mm (-0.3 to 0.9 mm)] in 24 patients (80%). An increased FD at the baseline was associated with significant growth during the 1-year follow-up in the proximal AA. An association was detected between decreased total wall shear stress and significant aortic growth in the inner curve of the sinotubular junction [529 mPa (449-664 mPa) vs 775 mPa (609-944 mPa); P = 0.03] and the anterior side of the proximal aortic arch [356 mPa (305-367 mPa) vs 493 mPa (390-586 mPa); P < 0.001]. CONCLUSIONS: FD and decreased wall shear stress seem to be associated with significant growth of AA dilatation at the 1-year follow-up. Thus, 4D flow MRI might be useful in assessing risk for AA diameter growth in patients with a tricuspid aortic valve.

Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice.

PURPOSE: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer. METHODS: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm2, respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential). RESULTS: Significant changes were observed in DWI data during the tumor growth, indicated by ADCm, ADCs, and ADCk. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model. CONCLUSION: Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.

Pulmonary Artery Dilatation Is a Common Finding in a Coronary Artery CT Angiography Population.

BACKGROUND/AIM: Dilatation of the main pulmonary artery (mPA) is a common incidental finding in chest imaging and often leads to consultation. The aim of this study was to determine the prevalence of mPA dilatation in a coronary artery CT angiography (CCTA) population. PATIENTS AND METHODS: The study investigated 985 consecutive patients scheduled for diagnostic CCTA. The transverse axial diameter of the mPA was measured. The prevalence of mPA dilatation was estimated using different reference values (Framingham Heart Study: 28.9 mm for males and 26.9 mm for females, Bozlar: 29.5 mm for both genders and Karazincir: 32.6 mm for males and 31.9 mm for females). RESULTS: The patient mean age was 53.0±9.7 years (66.5% were women). Body surface area (BSA) correlated moderately with the mPA diameter (r=0.423, p<0.001). The prevalence of mPA dilatation varied from 5.9% (Karazincir) to 33.7% (Framingham Heart Study) in the overall study population. CONCLUSION: The prevalence of mPA dilatation is high in a CCTA patient population when using a cut-off value from the Framingham Heart Study.

Lentivirus vector­mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain.

Translation of promising experimental therapies from rodent models to clinical success has been complicated as the novel therapies often fail in clinical trials. Existing rodent glioma models generally do not allow for preclinical evaluation of the efficiency of novel therapies in combination with surgical resection. Therefore, the aim of the present study was to develop a larger animal model utilizing lentivirus vector­mediated oncogenic transformation in the rabbit brain. Lentiviruses carrying constitutively active AKT and H­Ras oncogenes, and p53 small interfering (si)RNA were introduced into newborn rabbit neural stem cells (NSCs) and intracranially implanted into rabbits' brains to initiate tumor formation. In one of the ten rabbits a tumor was detected 48 days after the implantation of transduced NSCs. Histological features of the tumor mimic was similar to a benign Grade II ganglioglioma. Immunostaining demonstrated that the tissues were positive for AKT and H­Ras. Strong expression of GFAP and Ki­67 was also detected. Additionally, p53 expression was notably lower in the tumor area. The implantation of AKT, H­Ras and p53 siRNA transduced NSCs for tumor induction resulted in ganglioglioma formation. Despite the low frequency of tumor formation, this preliminary data provided a proof of principle that lentivirus vectors carrying oncogenes can be used for the generation of brain tumors in rabbits. Moreover, these results offer noteworthy insights into the pathogenesis of a rare brain tumor, ganglioglioma.

Whole Brain Adiabatic T1rho and Relaxation Along a Fictitious Field Imaging in Healthy Volunteers and Patients With Multiple Sclerosis: Initial Findings.

BACKGROUND: In preclinical models of multiple sclerosis (MS), both adiabatic T1rho (T1ρadiab ) and relaxation along a fictitious field (RAFF) imaging have demonstrated potential to noninvasively characterize MS. PURPOSE: To evaluate the feasibility of whole brain T1ρadiab and RAFF imaging in healthy volunteers and patients with MS. STUDY TYPE: Single institutional clinical trial. SUBJECTS: 38 healthy volunteers (24-69 years) and 21 patients (26-59 years) with MS. Five healthy volunteers underwent a second MR examination performed within 8 days. Clinical disease severity (The Expanded Disability Status Scale [EDSS] and The Multiple Sclerosis Severity Score [MSSS]) was evaluated at baseline and 1-year follow-up (FU). FIELD STRENGTH/SEQUENCE: RAFF in second rotating frame of reference (RAFF2) was performed at 3 T using 3D-fast-field echo with magnetization preparation, RF amplitude of 11.74 µT while the corresponding value for T1ρadiab was 13.50 µT. T1 -, T2 -, and FLAIR-weighted images were acquired with reconstruction voxel size 1.0 × 1.0 × 1.0 mm3 . ASSESSMENT: The parametric maps of T1ρadiab and RAFF2 (TRAFF2 ) were calculated using a monoexponential model. Semi-automatic segmentation of MS lesions, white matter (WM), and gray matter (GM), and WM tracks was performed using T1 -, T2 -, and FLAIR-weighted images. STATISTICAL TESTS: Regression analysis was used to evaluate correlation of T1ρadiab and TRAFF2 with age and disease severity while a Friedman test followed by Wilcoxon Signed Rank test for differences between tissue types. Short-term repeatability was evaluated on voxel level. RESULTS: Both T1ρadiab and TRAFF2 demonstrated good short-term repeatability with relative differences on voxel level in the range of 6.1%-11.9%. Differences in T1ρadiab and TRAFF2 between the tissue types in MS patients were significant (P < 0.05). T1ρadiab and TRAFF2 correlated (P < 0.001) with baseline EDSS/MSSM and disease progression at FU (P < 0.001). DATA CONCLUSION: Whole brain T1ρadiab and TRAFF2 at 3 T was feasible with significant differences in T1ρadiab and TRAFF2 values between tissues types and correlation with disease severity. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Docetaxel chemotherapy response in PC3 prostate cancer mouse model detected by rotating frame relaxations and water diffusion.

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times TRAFF2 and TRAFF4 than with the continuous wave T1ρ , adiabatic T1ρ , adiabatic T2ρ , T1 , T2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T1 and T2 , continuous wave T1ρ , adiabatic T1ρ and adiabatic T2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T2 -weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T1ρ, T2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T1 , while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published.