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1.  Clinical utility of endorectal MRI-guided prostate biopsy: Preliminary experience 
Purpose
To investigate the potential clinical utility of endorectal MRI-guided biopsy in patients with known or suspected prostate cancer.
Methods
We prospectively recruited 24 men with known or suspected prostate cancer in whom MRI-guided biopsy was clinically requested after multiparametric endorectal MRI showed one or more appropriate targets. One to six 18-gauge biopsy cores were obtained from each patient. Transrectal ultrasound guided biopsy results and post MRI-guided biopsy complications were also recorded.
Results
MRI-guided biopsy was positive in 5 of 7 patients with suspected prostate cancer (including 2 of 4 with prior negative ultrasound-guided biopsies), in 8 of 12 with known untreated prostate cancer (including 5 where MRI-guided biopsy demonstrated a higher Gleason score than ultrasound guided biopsy results), and in 3 of 5 with treated cancer. MRI-guided biopsies had a significantly higher maximum percentage of cancer in positive cores when compared to ultrasound guided biopsy (mean of 37 ± 8% versus 13 ± 4%; p = 0.01). No serious post-biopsy complications occurred.
Conclusion
Our preliminary experience suggests endorectal MRI-guided biopsy may safely contribute to the management of patients with known or suspected prostate cancer by making a new diagnosis of malignancy, upgrading previously diagnosed disease, or diagnosing local recurrence.
doi:10.1002/jmri.24383
PMCID: PMC4059791  PMID: 24924999
MR imaging; prostate biopsy; prostate cancer
2.  Optimized Breast MRI Functional Tumor Volume as a Biomarker of Recurrence-Free Survival Following Neoadjuvant Chemotherapy 
Purpose
To evaluate optimal contrast kinetics thresholds for measuring functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for assessment of recurrence-free survival (RFS).
Materials and Methods
In this Institutional Review Board (IRB)-approved retrospective study of 64 patients (ages 29–72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the breast. Tumor was defined as voxels meeting thresholds for early percent enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh); and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model determined associations between change in FTV over treatment and RFS at different PE and SER thresholds.
Results
The plot of hazard ratios for change in FTV from MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard ratio = 8.71, 95% confidence interval 2.86–25.5, P < 0.00015), indicating optimal model fit.
Conclusion
Enhancement thresholds affect the ability of MRI tumor volume to predict RFS. The value is robust over a wide range of thresholds, supporting the use of FTV as a biomarker.
doi:10.1002/jmri.24351
PMCID: PMC4507716  PMID: 24347097
SER/PE thresholds; MRI breast functional tumor volume; neoadjuvant chemotherapy
3.  Automatic Segmentation of Invasive Breast Carcinomas from DCE-MRI using Time Series Analysis 
Purpose
Quantitative segmentation methods based on black-box modeling and pharmacokinetic modeling are highly dependent on imaging pulse sequence, timing of bolus injection, arterial input function, imaging noise and fitting algorithms. To accurately segment invasive ductal carcinomas (IDCs) from dynamic contrast enhanced MRI (DCE-MRI) using time series analysis based on linear dynamic system (LDS) modeling.
Methods
We modeled the underlying dynamics of the tumor by a LDS and use the system parameters to segment the carcinoma on the DCE-MRI. Twenty-four patients with biopsy-proven IDCs were analyzed. The lesions segmented by the algorithm were compared with an expert radiologist’s segmentation and the output of a commercial software, CADstream. The results are quantified in terms of the accuracy and sensitivity of detecting the lesion and the amount of overlap, measured in terms of the Dice similarity coefficient (DSC).
Results
The segmentation algorithm detected the tumor with 90% accuracy and 100% sensitivity when compared to the radiologist’s segmentation and 82.1% accuracy and 100% sensitivity when compared to the CADstream output. The overlap of the algorithm output with the radiologist’s segmentation and CADstream output, computed in terms of the DSC was 0.77 and 0.72 respectively. The algorithm also shows robust stability to imaging noise. Simulated imaging noise with zero mean and standard deviation equal to 25% of the base signal intensity was added to the DCE-MRI series. The amount of overlap between the tumor maps generated by the LDS-based algorithm from the noisy and original DCE-MRI was DSC=0.95.
Conclusion
The time-series analysis based segmentation algorithm provides high accuracy and sensitivity in delineating the regions of enhanced perfusion corresponding to tumor from DCE-MRI.
doi:10.1002/jmri.24394
PMCID: PMC3962815  PMID: 24115175
DCE-MRI; Linear Dynamic System; Time-series analysis; Segmentation; Breast Carcinomas
4.  Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI 
Purpose
i) to validate Blood Oxygenation Level Dependent (BOLD) breath hold cerebrovascular reactivity mapping (BH CVR) as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional magnetic resonance imaging (fMRI) for sensorimotor mapping, and ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group.
Materials and Methods
We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional).
Results
Motor task mean T-value was significantly higher in the contralesional ROIs (6.00±1.74 vs 4.34±1.68, p=0.00004) as well as the BH mean T-value (4.74±2.30 vs 4.09±2.50, p=0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z=2.99, p=0.03). Actual NVU prevalence was 75%.
Conclusion
Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks).
doi:10.1002/jmri.24406
PMCID: PMC4009384  PMID: 24338845
fMRI; low grade gliomas; cerebrovascular reactivity mapping; neurovascular uncoupling
5.  Prediction of chemotherapeutic response in bladder cancer using k-means clustering of DCE-MRI pharmacokinetic parameters 
Purpose
To apply k-means clustering of two pharmacokinetic parameters derived from 3T DCE-MRI to predict chemotherapeutic response in bladder cancer at the mid-cycle time-point.
Materials and Methods
With the pre-determined number of 3 clusters, k-means clustering was performed on non-dimensionalized Amp and kep estimates of each bladder tumor. Three cluster volume fractions (VFs) were calculated for each tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline to mid-cycle were correlated with the tumor’s chemotherapeutic response. Receiver-operating-characteristics curve analysis was used to evaluate the performance of each cluster VF change as a biomarker of chemotherapeutic response in bladder cancer.
Results
k-means clustering partitioned each bladder tumor into cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3 (high kep and low Amp). The changes of all three cluster VFs were found to be associated with bladder tumor response to chemotherapy. The VF change of cluster 2 presented with the highest area-under-the-curve value (0.96) and the highest sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value.
Conclusion
k-means clustering of the two DCE-MRI pharmacokinetic parameters can characterize the complex microcirculatory changes within a bladder tumor to enable early prediction of the tumor’s chemotherapeutic response.
doi:10.1002/jmri.24663
PMCID: PMC4298475  PMID: 24943272
bladder cancer; chemotherapeutic response; k-means clustering; pharmacokinetic parameters
6.  Quantification of Left Ventricular Volumes, Mass and Ejection Fraction using Cine Displacement Encoding with Stimulated Echoes (DENSE) MRI 
Purpose
To test the hypothesis that magnitude images from cine Displacement Encoding with Stimulated Echoes (DENSE) MRI can accurately quantify left ventricular (LV) volumes, mass, and ejection fraction.
Materials and Methods
Thirteen mice (C57BL/6J) were imaged using a 7T ClinScan MRI. A short-axis stack of cine T2-weighted black blood (BB) images was acquired for calculation of left ventricular volumes, mass, and ejection fraction (EF) using the gold standard sum-of-slices methodology. DENSE images were acquired during the same imaging session in three short-axis (basal, mid, apical) and two long-axis orientations. A custom surface fitting algorithm was applied to epicardial and endocardial borders from the DENSE magnitude images to calculate volumes, mass, and EF. Agreement between the DENSE-derived measures and BB-derived measures was assessed via coefficient of variation (CoV).
Results
3D surface reconstruction was completed on the order of seconds from segmented images, and required fewer slices to be segmented. Volumes, mass, and EF from DENSE-derived surfaces matched well with BB data (CoVs ≤11%).
Conclusion
LV mass, volumes, and ejection fraction in mice can be quantified through sparse (5 slices) sampling with DENSE. This consolidation significantly reduces the time required to assess both mass/volume-based measures of cardiac function and advanced cardiac mechanics.
doi:10.1002/jmri.24350
PMCID: PMC4311752  PMID: 24923710
magnetic resonance imaging; DENSE; ventricular volume and mass; heart
7.  MRI Methods for Evaluating the Effects of Tyrosine Kinase Inhibitor Administration Used to Enhance Chemotherapy Efficiency in a Breast Tumor Xenograft Model 
Purpose
To evaluate whether quantitative MRI parameters are sensitive to the effects of the tyrosine kinase inhibitor gefitinib and can discriminate between two different treatment protocols.
Materials and Methods
Untreated mice with BT474 breast tumor xenografts were characterized in a preliminary study. Subsequently, tumor volume, apparent diffusion coefficient (ADC), transendothelial permeability (Kps), and fractional plasma volume (fPV) were measured in three groups of mice receiving: 1) control vehicle for 10 days, or gefitinib as 2) a single daily dose for 10 days or 3) a 2-day pulsed dose.
Results
Gefitinib treatment resulted in significant tumor growth inhibition (pulsed: 439 ± 93; daily: 404 ± 53; control: 891 ± 174 mm3, P < 0.050) and lower cell density (pulsed: 0.15 ± 0.01, daily: 0.17 ± 0.01, control: 0.24 ± 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but decreased in controls (P > 0.050). Tumor Kps decreased with pulsed treatment but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor fPV increased in both treated groups, decreasing afterwards with pulsed treatment (P > 0.050).
Conclusion
Quantitative MRI can provide a sensitive measure of gefitinib-induced tumor changes, potentially distinguish between treatment regimens, and may be useful for determining optimal treatment scheduling for enhancing chemotherapy delivery.
doi:10.1002/jmri.21737
PMCID: PMC4511711  PMID: 19388114
chemotherapy; dynamic contrast enhanced; diffusion weighted imaging; gefitinib; tyrosine kinase inhibitor; xenograft tumor model
8.  Quantification of Superparamagnetic Iron Oxide (SPIO)-labeled Cells Using MRI 
Purpose
To show the feasibility of using magnetic resonance imaging (MRI) to quantify superparamagnetic iron oxide (SPIO)-labeled cells.
Materials and Methods
Lymphocytes and 9L rat gliosarcoma cells were labeled with Ferumoxides-Protamine Sulfate complex (FE-PRO). Cells were labeled efficiently (more than 95%) and iron concentration inside each cell was measured by spectrophotometry (4.77-30.21 picograms). Phantom tubes containing different number of labeled or unlabeled cells as well as different concentrations of FE-PRO were made. In addition, labeled and unlabeled cells were injected into fresh and fixed rat brains.
Results
Cellular viability and proliferation of labeled and unlabeled cells were shown to be similar. T2-weighted images were acquired using 7 T and 3 T MRI systems and R2 maps of the tubes containing cells, free FE-PRO, and brains were made. There was a strong linear correlation between R2 values and labeled cell numbers but the regression lines were different for the lymphocytes and gliosarcoma cells. Similarly, there was strong correlation between R2 values and free iron. However, free iron had higher R2 values than the labeled cells for the same concentration of iron.
Conclusion
Our data indicated that in vivo quantification of labeled cells can be done by careful consideration of different factors and specific control groups.
doi:10.1002/jmri.20978
PMCID: PMC4509786  PMID: 17623892
Magnetic Resonance Imaging (MRI); Magnetically Labeled Cells; Quantification; Reproducibility; Superparamagnetic Iron Oxide (SPIO)
9.  Functional magnetic resonance imaging in conscious rats using a chronically implanted surface coil 
Purpose
To establish procedures for functional magnetic resonance imaging in rats without the need for anaesthetic agents.
Materials and Methods
Rats were trained to habituate to restraint in a harness and scanner noise. Under anaesthesia, rats were then prepared with a cranial implant that permitted stabilization of the head during subsequent imaging experiments. The cranial implant included an RF coil that was used to transmit and receive radiofrequency signals during imaging. Further training was then conducted to habituate the animals to head fixation whilst in the MR scanner.
Results
Using this method, we were able to successfully and repeatedly record BOLD fMRI responses to hypercapnia and whisker stimulation in awake rats. Electrical stimulation of the whisker pad produced a ~7% increase in BOLD signal in the corresponding barrel cortex as well as adjacent negative BOLD responses, whilst hypercapnia produced larger increases in BOLD signal amplitude.
Conclusion
This methodology leaves the face and limbs free from obstruction, making possible a range of behavioural or sensory stimulation protocols. Further development of this animal model could enable traditional behavioural neuroscience techniques to be combined with modern functional neuroimaging.
doi:10.1002/jmri.23914
PMCID: PMC4500943  PMID: 23677870
Functional magnetic resonance imaging; rat; anaesthesia
10.  Effects of Receive-Only Inserts on SAR, B1+ Field and Tx Coil Performance 
Purpose
To evaluate the effect of different cylindrical and close conforming receive only array designs on spin excitation and specific absorption rate (SAR) of a 7 Tesla transmit only head coil.
Materials and Methods
We developed FDTD models of different receive only array geometries. Cylindrical and close fitting helmet arrays with varying copper trace widths; a TEM Tx coil model and two head models were used in numerical simulations. Tx coil coupling was experimentally measured and validated with FDTD modeling.
Results
Changing copper trace width of loops in array models caused subtle changes in RF absorption (<5%). Changes in SAR distribution were observed in the head models with Rx-only inserts. Peak SAR increased (−1 to +15%) in different tissues for a mean B1+ in the brain of 2 μT. Total absorption in the head models for 1 Watt forward power increased (5 to 21%) in the heads with Rx-only inserts. Changes in RF absorption with different Rx-inserts indicate a change in RF radiation of the Tx coil even when changes in B1+ and coupling between ports of Tx coil were minimal.
Conclusion
Changes in local/global SAR and subtle changes in B1+ field distributions were observed with the presence of Rx-only inserts. Thus, incorporation of the receive-only array effects are needed when evaluating SAR and designing RF transmit pulse waveform parameters for shimming and/or Tx-SENSE for 7 T MRI.
doi:10.1002/jmri.24152
PMCID: PMC4501854  PMID: 23913474
RECEIVE ARRAYS; B1 FIELD AND SAR; RF MODELING
11.  Diffusion Tensor Tractography of the Human Brain Cortico-Ponto-Cerebellar Pathways: A Quantitative Preliminary Study 
Purpose
To investigate the utility of diffusion tensor tractography at 1mm slice thickness to map and quantify the whole trajectory of different cortico-ponto-cerebellar pathways of the healthy adult human brain.
Materials and Methods
This work was approved by the local Institutional Review Board, and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Five healthy right-handed men (age range, 24–37 years) were studied and written informed consent was obtained. Diffusion tensor imaging data acquired with 1-mm slice thickness at a 3.0 Tesla (T) clinical MRI scanner were prepared and analyzed using tractography methods to reconstruct the cortico-ponto-cerebellar pathways which included the fronto-ponto-cerebellar, parieto-ponto-cerebellar, occipitoponto- cerebellar, and temporo-ponto-cerebellar tracts.
Results
We demonstrate the feasibility of tractographic mapping and quantification of the four cortico-ponto-cerebellar system components based on their cortical connections in the healthy human brain using DTI data with thin 1-mm sections.
Conclusion
In vivo quantification of different corticoponto-cerebellar pathways based on cortical connection is feasible, using 1-mm slices at 3.0T.
doi:10.1002/jmri.22330
PMCID: PMC4492525  PMID: 20882611
diffusion tensor imaging; tractography; thin slices; cortico-ponto-cerebellar pathways
12.  A fully automated tool to identify the aorta and compute flow using Phase-contrast MRI: validation and application in a large population based study 
Purpose
To assess if fully automated localization of the aorta can be achieved using phase contrast (PC) magnetic resonance (MR) images.
Materials and Methods
PC cardiac gated MR images were obtained as part of a large population-based study. A fully automated process using the Hough transform was developed to localize the ascending aorta (AAo) and descending aorta (DAo). The study was designed to validate this technique by determining: 1) its performance in localizing the AAo and DAo; 2) its accuracy in generating AAo flow volume and DAo flow volume; and 3) its robustness on studies with pathological abnormalities or imaging artifacts.
Results
The algorithm was applied successfully on 1,884 participants. In the randomly selected 50-study validation set, linear regression shows an excellent correlation between the automated (A) and manual (M) methods for AAo flow (r = 0.99) and DAo flow (r = 0.99). Bland-Altman difference analysis demonstrates strong agreement with minimal bias for: AAo flow (mean difference (A-M) = 0.47 ± 2.53 ml), and DAo flow (mean difference (A-M) = 1.74 ± 2.47 ml).
Conclusion
A robust fully automated tool to localize the aorta and provide flow volume measurements on phase contrast MRI was validated on a large population-based study.
doi:10.1002/jmri.24338
PMCID: PMC3969872  PMID: 24115597
automatic; localization; phase contrast; aorta; segmentation
13.  Feasibility of 3-D MRI of Proximal Femur Microarchitecture at 3 T using 26 Receive Elements without and with Parallel Imaging 
Purpose
High-resolution imaging of deeper anatomy such as the hip is challenging due to low signal-to-noise ratio (SNR), necessitating long scan times. Multi-element coils can increase SNR and reduce scan time through parallel imaging (PI). We assessed the feasibility of using a 26-element receive coil setup to perform 3 T MRI of proximal femur microarchitecture without and with PI.
Materials and Methods
This study had institutional review board approval. We scanned thirteen subjects on a 3 T scanner using 26 receive-elements and a 3-D FLASH sequence without and with PI (acceleration factors (AF) 2, 3, 4). We assessed SNR, depiction of individual trabeculae, PI performance (1/g-factor), and image quality with PI (1=non-visualization to 5=excellent).
Results
SNR maps demonstrate higher SNR for the 26-element setup compared to a 12-element setup for hip MRI. Without PI, individual proximal femur trabeculae were well-depicted, including microarchitectural deterioration in osteoporotic subjects. With PI, 1/g values for the 26-element/12-element receive-setup were 0.71/0.45, 0.56/0.25, and 0.44/0.08 at AF2, AF3, and AF4, respectively. Image quality was: AF1, excellent (4.8±0.4); AF2, good (4.2±1.0); AF3, average (3.3±1.0); AF4, non-visualization (1.4±0.9).
Conclusion
A 26-element receive-setup permits 3 T MRI of proximal femur microarchitecture with good image quality up to PI AF2.
doi:10.1002/jmri.24345
PMCID: PMC4004721  PMID: 24711013
Bone microarchitecture; hip; femoral neck; fracture; MRI; osteoporosis
14.  Reduction of Motion Artifacts in Carotid MRI using FID Navigators 
Purpose
To develop a framework for prospective free-induction decay (FID) based navigator gating for suppression of motion artifacts in carotid MRI and to assess its capability in-vivo.
Methods
An FID-navigator, comprising a spatially-selective low flip-angle sinc-pulse followed by an ADC-readout, was added to a conventional turbo spin-echo (TSE) sequence. Real-time navigator processing delivered accept/reject-and-reacquire decisions to the sequence. In this IRB-approved study, seven volunteers were scanned with a 2D T2-weighted TSE sequence. A reference scan with volunteers instructed to minimize motion as well as non-gated and gated scans with volunteers instructed to perform different motion tasks were performed in each subject. Multiple image quality measures were employed to quantify the effect of gating.
Results
There was no significant difference in lumen-to-wall sharpness (2.3±0.3 vs. 2.3±0.4), contrast-to-noise ratio (CNR) (9.0±2.0 vs. 8.5±2.0) or image quality score (3.1±0.9 vs. 2.6±1.2) between the reference and gated images. For images acquired during motion, all image quality measures were higher (p < 0.05) in the gated compared to non-gated images (Sharpness: 2.3±0.4 vs. 1.8±0.5, CNR: 8.5±2.0 vs. 7.2±2.0, score: 2.6±1.2 vs. 1.8±1.0).
Conclusion
Artifacts caused by the employed motion tasks deteriorated image quality in the non-gated scans. These artifacts were alleviated with the proposed FID-navigator.
doi:10.1002/jmri.24389
PMCID: PMC4019716  PMID: 24677562
Carotid MRI; Motion Compensation; FID Navigator; Motion Suppression; Carotid Artery Disease; Atherosclerosis
15.  DCE-MRI of the liver: effect of linear and non linear conversions on hepatic perfusion quantification and reproducibility 
Purpose
To evaluate the effect of different methods to convert MR signal intensity (SI) to gadolinium concentration ([Gd]) on estimation and reproducibility of model-free and modeled hepatic perfusion parameters measured with DCE-MRI.
Materials and Methods
In this IRB-approved prospective study, 23 DCE-MRI examinations of the liver were performed on 17 patients. SI was converted to [Gd] using linearity vs. non linearity assumptions (using SPGR signal equations). [Gd] vs. time curves were analyzed using model-free parameters and a dual-input single compartment model. Perfusion parameters obtained with the two conversion methods were compared using paired Wilcoxon test. Test-retest and inter-observer reproducibility of perfusion parameters were assessed in 6 patients.
Results
There were significant differences between the two conversion methods for the following parameters: AUC60 (area under the curve at 60 seconds, p <0.001), peak gadolinium concentration (Cpeak, p <0.001), upslope (p <0.001), Fp (portal flow, p=0.04), total hepatic flow (Ft, p=0.007), and MTT (mean transit time, p <0.001). Our preliminary results showed acceptable to good reproducibility for all model-free parameters for both methods [mean coefficient of variation (CV) range, 11.87–23.7%], except for upslope (CV = 37%). Among modeled parameters, DV (distribution volume) had CV <22% with both methods, PV and MTT showed CV <21% and <29% using SPGR equations, respectively. Other modeled parameters had CV >30% with both methods.
Conclusion
Linearity assumption is acceptable for quantification of model-free hepatic perfusion parameters while the use of SPGR equations and T1 mapping may be recommended for the quantification of modeled hepatic perfusion parameters.
doi:10.1002/jmri.24341
PMCID: PMC4058642  PMID: 24923476
Liver; perfusion quantification; fibrosis
16.  Clinical Performance of Contrast Enhanced Abdominal Pediatric MRI with Fast Combined Parallel Imaging Compressed Sensing Reconstruction 
Purpose
To deploy clinically, a combined parallel imaging compressed sensing method with coil compression that achieves a rapid image reconstruction, and assess its clinical performance in contrast-enhanced abdominal pediatric MRI.
Materials and Methods
With IRB approval and informed patient consent/assent, 29 consecutive pediatric patients were recruited. Dynamic contrast-enhanced MRI was acquired on a 3T scanner using a dedicated 32-channel pediatric coil and a 3D SPGR sequence, with pseudo-random undersampling at a high acceleration (R=7.2). Undersampled data were reconstructed with three methods: a traditional parallel imaging method and a combined parallel imaging compressed sensing method with and without coil compression. The three sets of images were evaluated independently and blindly by two radiologists at one siting, for overall image quality and delineation of anatomical structures. Wilcoxon tests were performed to test the hypothesis that there was no significant difference in the evaluations, and inter-observer agreement was analyzed.
Results
Fast reconstruction with coil compression did not deteriorate image quality. The mean score of structural delineation of the fast reconstruction was 4.1 on a 5-point scale, significantly better (P<0.05) than traditional parallel imaging (mean score 3.1). Fair to substantial inter-observer agreement was reached in structural delineation assessment.
Conclusion
A fast combined parallel imaging compressed sensing method is feasible in a pediatric clinical setting. Preliminary results suggest it may improve structural delineation over parallel imaging.
doi:10.1002/jmri.24333
PMCID: PMC3984374  PMID: 24127123
Contrast-enhanced abdominal pediatric MRI; Coil compression; Parallel imaging; Compressed sensing
17.  Magnetic Resonance Imaging Hemodynamic Markers of Progressive Bicuspid Aortic Valve Related Aortic Disease 
Purpose
To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV).
Materials and Methods
25 patients previously studied with 4D Flow imaging who had at least 2 separate cross-sectional imaging studies to assess for aortic growth were included: tricuspid aortic valve (TAV) controls without valvular disease (n = 12) and patients with BAV (n = 13). Flow data from the ascending aorta was used for calculation of peak velocity, normalized flow displacement, maximum wall shear stress (WSS), mean WSS, and minimal WSS. Pearson’s correlation was used to evaluate inter-observer agreement, and linear regression to evaluate the correlation between the different hemodynamic markers and growth. Patient informed consent was waived by the institutional review board that approved the study.
Results
Peak velocity and flow displacement were very reproducible (r = 0.90–1.0 and r = 0.91–0.98, respectively). The range of WSS parameters was largely reproducible (0.47 < r < 0.96) with the greatest variability at the data extraction stage of analysis (0.47 < r < 0.85). Flow displacement best correlated with interval aortic growth (r = 0.65), peak velocity was moderately correlated (r = 0.35), but the WSS parameters did not correlate well with growth (r < 0.17).
Conclusion
Flow displacement is a simple and reproducible hemodynamic marker that shows good correlation with aortic growth in patients with bicuspid aortic valves.
doi:10.1002/jmri.24362
PMCID: PMC4010553  PMID: 24788592
MRI; Aorta; Valves; BAV; Eccentric Jets
18.  Fast Image Reconstruction with L2-Regularization 
Purpose
We introduce L2-regularized reconstruction algorithms with closed-form solutions that achieve dramatic computational speed-up relative to state of the art L1- and L2-based iterative algorithms while maintaining similar image quality for various applications in MRI reconstruction.
Materials and Methods
We compare fast L2-based methods to state of the art algorithms employing iterative L1- and L2-regularization in numerical phantom and in vivo data in three applications; 1) Fast Quantitative Susceptibility Mapping (QSD), 2) Lipid artifact suppression in Magnetic Resonance Spectroscopic Imaging (MRSI), and 3) Diffusion Spectrum Imaging (DSI). In all cases, proposed L2-based methods are compared with the state of the art algorithms, and two to three orders of magnitude speed up is demonstrated with similar reconstruction quality.
Results
The closed-form solution developed for regularized QSM allows processing of a 3D volume under 5 seconds, the proposed lipid suppression algorithm takes under 1 second to reconstruct single-slice MRSI data, while the PCA based DSI algorithm estimates diffusion propagators from undersampled q-space for a single slice under 30 seconds, all running in Matlab using a standard workstation.
Conclusion
For the applications considered herein, closed-form L2-regularization can be a faster alternative to its iterative counterpart or L1-based iterative algorithms, without compromising image quality.
doi:10.1002/jmri.24365
PMCID: PMC4106040  PMID: 24395184
regularization; susceptibility mapping; diffusion imaging; spectroscopic imaging; lipid suppression
19.  T2 Relaxation Time Quantitation Differs Between Pulse Sequences in Articular Cartilage 
Background
To compare T2 relaxation time measurements between MR pulse sequences at 3 Tesla in agar phantoms and in vivo patellar, femoral, and tibial articular cartilage.
Methods
T2 relaxation times were quantified in phantoms and knee articular cartilage of eight healthy individuals using a single echo spin echo (SE) as a reference standard and five other pulse sequences: multi-echo SE (MESE), fast SE (2D-FSE), magnetization-prepared spoiled gradient echo (3D-MAPSS), three-dimensional (3D) 3D-FSE with variable refocusing flip angle schedules (3D vfl-FSE), and quantitative double echo steady state (qDESS). Cartilage was manually segmented and average regional T2 relaxation times were obtained for each sequence. A regression analysis was carried out between each sequence and the reference standard, and root-mean-square error (RMSE) was calculated.
Results
Phantom measurements from all sequences demonstrated strong fits (R2>0.8; P<0.05). For in vivo cartilage measurements, R2 values, slope, and RMSE were: MESE: 0.25/0.42/5.0 ms, 2D-FSE: 0.64/1.31/9.3 ms, 3D-MAPSS: 0.51/0.66/3.8 ms, 3D vfl-FSE: 0.30/ 0.414.2 ms, qDESS: 0.60/0.90/4.6 ms.
Conclusion
2D-FSE, qDESS, and 3D-MAPSS demonstrated the best fits with SE measurements as well as the greatest dynamic ranges. The 3D-MAPSS, 3D vfl-FSE, and qDESS demonstrated the closest average measurements to SE. Discrepancies in T2 relaxation time quantitation between sequences suggest that care should be taken when comparing results between studies.
doi:10.1002/jmri.24757
PMCID: PMC4369475  PMID: 25244647
cartilage; magnetic resonance imaging; T2 relaxation time mapping; pulse sequence
20.  Susceptibility-Weighted Imaging and Quantitative Susceptibility Mapping in the Brain 
Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging.
doi:10.1002/jmri.24768
PMCID: PMC4406874  PMID: 25270052
MRI; magnetic resonance imaging; SWI; susceptibility weighted imaging; STI; susceptibility tensor imaging; QSM; quantitative susceptibility mapping; MSA; magnetic susceptibility anisotropy; hemorrhage; iron; myelin; TBI; traumatic brain injury; multiple sclerosis; stroke
21.  Robust GRAPPA Reconstruction and Its Evaluation With the Perceptual Difference Model 
Purpose
To develop and optimize a new modification of GRAPPA (generalized autocalibrating partially parallel acquisitions) MR reconstruction algorithm named “Robust GRAPPA”.
Materials and Methods
In Robust GRAPPA, k-space data points were weighted before the reconstruction. Small or zero weights were assigned to “outliers” in k-space. We implemented a Slow Robust GRAPPA method, which iteratively reweighted the k-space data. It was compared to an ad hoc Fast Robust GRAPPA method, which eliminated (assigned zero weights to) a fixed percentage of k-space “outliers” following an initial estimation procedure. In comprehensive experiments the new algorithms were evaluated using the perceptual difference model (PDM), whereby image quality was quantitatively compared to the reference image. Independent variables included algorithm type, total reduction factor, outlier ratio, center filling options, and noise across multiple image datasets, providing 10,800 test images for evaluation.
Results
The Fast Robust GRAPPA method gave results very similar to Slow Robust GRAPPA, and showed significant improvements as compared to regular GRAPPA. Fast Robust GRAPPA added little computation time compared with regular GRAPPA.
Conclusion
Robust GRAPPA was proposed and proved useful for improving the reconstructed image quality. PDM was helpful in designing and optimizing the MR reconstruction algorithms.
doi:10.1002/jmri.21352
PMCID: PMC4484794  PMID: 18504764
GRAPPA; parallel imaging; robust fitting; PDM
22.  Magnetization Transfer (MT) Asymmetry Around the Water Resonance in Human Cervical Spinal Cord 
Purpose
To demonstrate the presence of MT asymmetry in human cervical spinal cord due to the interaction between bulk water and semisolid macromolecules (conventional MT), and the chemical exchange dependent saturation transfer (CEST) effect.
Materials and methods
MT asymmetry in the cervical spinal cord (C3/C4 - C5) was investigated in 14 healthy male subjects with a 3T magnetic resonance (MR) system. Both spin-echo (SE) and gradient-echo (GE) echo-planar imaging (EPI) sequences, with low power off-resonance radiofrequency irradiation at different frequency offsets, were used.
Results
Our results show that the z-spectrum in gray/white matter is asymmetrical about the water resonance frequency in both SE-EPI and GE-EPI, with a more significant saturation effect at the lower frequencies (negative frequency offset) far away from water and at the higher frequencies (positive offset) close to water. These are attributed mainly to the conventional MT and CEST effects respectively. Furthermore, the amplitude of MT asymmetry is larger in SE-EPI sequence than in GE-EPI sequence in the frequency range of amide protons.
Conclusion
Our results demonstrate the presence of MT asymmetry in human cervical spinal cord, which is consistent with the ones reported in the brain.
doi:10.1002/jmri.21610
PMCID: PMC4485611  PMID: 19243033
magnetization transfer; asymmetry; CEST; APT; spinal cord
23.  Parallel MR Imaging 
Parallel imaging is a robust method for accelerating the acquisition of magnetic resonance imaging (MRI) data, and has made possible many new applications of MR imaging. Parallel imaging works by acquiring a reduced amount of k-space data with an array of receiver coils. These undersampled data can be acquired more quickly, but the undersampling leads to aliased images. One of several parallel imaging algorithms can then be used to reconstruct artifact-free images from either the aliased images (SENSE-type reconstruction) or from the under-sampled data (GRAPPA-type reconstruction). The advantages of parallel imaging in a clinical setting include faster image acquisition, which can be used, for instance, to shorten breath-hold times resulting in fewer motion-corrupted examinations. In this article the basic concepts behind parallel imaging are introduced. The relationship between undersampling and aliasing is discussed and two commonly used parallel imaging methods, SENSE and GRAPPA, are explained in detail. Examples of artifacts arising from parallel imaging are shown and ways to detect and mitigate these artifacts are described. Finally, several current applications of parallel imaging are presented and recent advancements and promising research in parallel imaging are briefly reviewed.
doi:10.1002/jmri.23639
PMCID: PMC4459721  PMID: 22696125
SENSE; GRAPPA; parallel imaging; fast imaging
24.  Early Therapy Assessment of Combined Anti-DR5 Antibody and Carboplatin in Triple-Negative Breast Cancer Xenografts in Mice Using Diffusion-Weighted Imaging and 1H MR Spectroscopy 
Purpose
To assess the early response of triple-negative breast-cancer (TNBC) following TRA-8 and carboplatin therapy using DWI and MRS in 2LMP and SUM159 mouse models.
Materials and Methods
Four groups (n = 5/group) of each model were untreated or treated with carboplatin, TRA-8, and combination, respectively. DWI and MRS were applied on 0, 3, and 7 days after therapy initiation, and all tumors were collected thereafter for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. The changes in intratumoral apparent diffusion coefficient (ADC) and fat–water ratios (FWRs) were compared with tumor volume changes and apoptotic cell densities.
Results
Mean ADC values of 2LMP and SUM159 tumors significantly increased 4 ± 4% and 37 ± 11% during 7 days of combination therapy, respectively, as compared to control groups (P < 0.05). Similarly, mean FWRs of 2LMP and SUM159 tumors significantly increased 102 ± 30% and 126 ± 52%, respectively, for 7 days of combined treatment (P < 0.05). The changes of the mean ADC values for 3 days (or FWRs for 7 days) were linearly proportional to either the mean volume changes or apoptotic cell densities in both models.
Conclusion
DWI and MRS assessed the early tumor response to TRA-8 and carboplatin in TNBC mouse models.
doi:10.1002/jmri.24319
PMCID: PMC4076049  PMID: 24151215
DWI; MRS; TRA-8; carboplatin; triple-negative breast cancer
25.  MRI of the Hip at 7 Tesla: Feasibility of Bone Microarchitecture, High-Resolution Cartilage, and Clinical Imaging 
Purpose
To demonstrate the feasibility of performing bone microarchitecture, high- resolution cartilage, and clinical imaging of the hip at 7 Tesla.
Materials and Methods
This study had institutional review board approval. Using an 8-channel coil constructed in-house, we imaged the hips of 15 subjects on a 7 T MRI scanner. We applied: 1) a T1-weighted 3-dimensional fast low angle shot (3-D FLASH) sequence (0.23 × 0.23 × 1–1.5 mm3) for bone microarchitecture imaging; 2) T1-weighted 3-D FLASH (water excitation) and volumetric interpolated breath-hold examination (VIBE) sequences (0.23 × 0.23 × 1.5 mm3) with saturation or inversion recovery-based fat suppression for cartilage imaging; 3) 2-D intermediate-weighted fast spin-echo (FSE) sequences without and with fat saturation (0.27 mm × 0.27 mm × 2 mm) for clinical imaging.
Results
Bone microarchitecture images allowed visualization of individual trabeculae within the proximal femur. Cartilage was well-visualized and fat was well-suppressed on FLASH and VIBE sequences. FSE sequences allowed visualization of cartilage, the labrum (including cartilage and labral pathology), joint capsule, and tendons.
Conclusion
This is the first study to demonstrate the feasibility of performing a clinically-comprehensive hip MRI protocol at 7 T, including high-resolution imaging of bone microarchitecture and cartilage, as well as clinical imaging.
doi:10.1002/jmri.24305
PMCID: PMC3962810  PMID: 24115554
7 Tesla; MRI; hip; bone microarchitecture; cartilage; clinical

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