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Time-dependent diffusion in skeletal muscle with the random permeable barrier model (RPBM): application to normal controls and chronic exertional compartment syndrome patients
Sigmund, Eric E; Novikov, Dmitry S; Sui, Dabang; Ukpebor, Obehi; Baete, Steven; Babb, James S; Liu, Kecheng; Feiweier, Thorsten; Kwon, Jane; McGorty, Kellyanne; Bencardino, Jenny; Fieremans, Els
The purpose of this work was to carry out diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Using an institutional review board approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3 T scanner at rest and after treadmill exertion at four different Td values. Radial diffusion values lambdarad were computed for each of seven different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D0 , fiber diameter a, and permeability kappa. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D0 showed significant (p < 0.05) increases with exercise for volunteers, and a increased significantly (p < 0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p = 0.07), and larger permeability increases (p = 0.07) than controls. Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy
PMCID:3980069
PMID: 24610770
ISSN: 0952-3480
CID: 875412
New magnetic resonance imaging methods in nephrology
Zhang, Jeff L; Morrell, Glen; Rusinek, Henry; Sigmund, Eric E; Chandarana, Hersh; Lerman, Lilach O; Prasad, Pottumarthi V; Niles, David; Artz, Nathan; Fain, Sean; Vivier, Pierre-Hugues; Cheung, Alfred K; Lee, Vivian S
Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury, and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics.
PMCID:3965662
PMID: 24067433
ISSN: 0085-2538
CID: 900422
Multiple-echo diffusion tensor acquisition technique (MEDITATE) on a 3T clinical scanner
Baete, Steven H; Cho, Gene; Sigmund, Eric E
This article describes the concepts and implementation of an MRI method, the multiple-echo diffusion tensor acquisition technique (MEDITATE), which is capable of acquiring apparent diffusion tensor maps in two scans on a 3T clinical scanner. In each MEDITATE scan, a set of RF pulses generates multiple echoes, the amplitudes of which are diffusion weighted in both magnitude and direction by a pattern of diffusion gradients. As a result, two scans acquired with different diffusion weighting strengths suffice for accurate estimation of diffusion tensor imaging (DTI) parameters. The MEDITATE variation presented here expands previous MEDITATE approaches to adapt to the clinical scanner platform, such as exploiting longitudinal magnetization storage to reduce T2 weighting. Fully segmented multi-shot Cartesian encoding is used for image encoding. MEDITATE was tested on isotropic (agar gel), anisotropic diffusion phantoms (asparagus) and in vivo skeletal muscle in healthy volunteers with cardiac gating. Comparisons of accuracy were performed with standard twice-refocused spin echo (TRSE) DTI in each case and good quantitative agreement was found between diffusion eigenvalues, mean diffusivity and fractional anisotropy derived from TRSE DTI and from the MEDITATE sequence. Orientation patterns were correctly reproduced in both isotropic and anisotropic phantoms, and approximately for in vivo imaging. This illustrates that the MEDITATE method of compressed diffusion encoding is feasible on the clinical scanner platform. With future development and employment of appropriate view-sharing image encoding, this technique may be used in clinical applications requiring time-sensitive acquisition of DTI parameters such as dynamical DTI in muscle
PMCID:3800503
PMID: 23828606
ISSN: 0952-3480
CID: 586182
Stimulated echo diffusion tensor imaging and SPAIR T(2) -weighted imaging in chronic exertional compartment syndrome of the lower leg muscles
Sigmund, Eric E; Sui, Dabang; Ukpebor, Obehi; Baete, Steven; Fieremans, Els; Babb, James S; Mechlin, Michael; Liu, Kecheng; Kwon, Jane; McGorty, Kellyanne; Hodnett, Philip A; Bencardino, Jenny
PURPOSE: To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T(2) -weighted (T2w) imaging. MATERIALS AND METHODS: Using an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2w imaging and stimulated echo DTI were applied to eight healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in seven calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post/pre-exercise ratios) of DTI parameters. RESULTS: All diffusivities significantly increased (P < 0.0001) and FA decreased (P = 0.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (P < 0.0001). Nineteen of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8 +/- 3.4% (volunteer), 7.4 +/- 4.2% (normal), and 9.1 +/- 7.0% (CECS) with exercise. CONCLUSION: DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment. J. Magn. Reson. Imaging 2013;. (c) 2013 Wiley Periodicals, Inc.
PMCID:3664655
PMID: 23440764
ISSN: 1053-1807
CID: 231572
Utility of diffusional kurtosis imaging as a marker of adverse pathologic outcomes among prostate cancer active surveillance candidates undergoing radical prostatectomy
Rosenkrantz, Andrew B; Prabhu, Vinay; Sigmund, Eric E; Babb, James S; Deng, Fang-Ming; Taneja, Samir S
OBJECTIVE. The purpose of this study was to compare findings at nongaussian diffusional kurtosis imaging and conventional diffusion-weighted MRI as markers of adverse pathologic outcomes among prostate cancer patients who are active surveillance candidates and choose to undergo prostatectomy. MATERIALS AND METHODS. Fifty-eight active surveillance candidates (prostate-specific antigen concentration, < 10 ng/mL; clinical tumor category less than T2a; Gleason score, 3 + 3; = 25% of biopsy cores positive for tumor; = 50% tumor involvement of any individual core; = 20% tumor involvement across all cores) who underwent prostatectomy and preoperative 3-T MRI including diffusional kurtosis imaging (b values, 0, 500, 1000, 1500, and 2000 s/mm(2)) were included. Adverse pathologic features at prostatectomy were defined using two schemes of varying stringency. One scheme (less stringent) was presence of a Gleason score greater than 6 or extracapsular extension (n = 19). The other scheme (more stringent) was presence of a Gleason score greater than 6, extracapsular extension, or an index tumor 10 mm or larger (n = 35). Parametric maps displaying standard apparent diffusion coefficient (ADC), kurtosis (K) representing nongaussian diffusion behavior, and diffusion (D) representing a diffusion coefficient adjusted for nongaussian (kurtosis) behavior were reviewed, and the most abnormal region was recorded for each metric. Associations between these metrics and the presence of adverse final pathologic findings were assessed with unpaired Student t tests and receiver operating characteristic analyses. RESULTS. For both schemes, only D was significantly lower in patients with adverse final pathologic findings (p = 0.006, p = 0.025). K tended to be greater in patients with adverse final pathologic findings for the more stringent scheme (p = 0.072). ADC was not significantly different in the presence of adverse final pathologic findings for either scheme (p = 0.357, p = 0.383). With either scheme, D had a larger area under the receiver operating characteristics curve (AUC) for predicting adverse final pathologic results (AUC, 0.691 and 0.743) than did ADC (AUC, 0.569 and 0.655) or K (AUC, 0.617 and 0.714), but the difference was not significant (p = 0.183, p = 0.734). CONCLUSION. Preliminary results suggest that diffusional kurtosis imaging findings may have more value than findings at conventional diffusion-weighted MRI as a marker of adverse final pathologic outcome among active surveillance candidates.
PMID: 24059373
ISSN: 0361-803x
CID: 542842
Ductal Carcinoma in Situ of the Breasts: Review of MR Imaging Features
Greenwood, Heather I; Heller, Samantha L; Kim, Sungheon; Sigmund, Eric E; Shaylor, Sara D; Moy, Linda
The incidence of ductal carcinoma in situ (DCIS) has increased over the past few decades and now accounts for over 20% of newly diagnosed cases of breast cancer. Although the detection of DCIS has increased with the advent of widespread mammography screening, it is essential to have a more accurate assessment of the extent of DCIS for successful breast conservation therapy. Recent studies evaluating the detection of DCIS with magnetic resonance (MR) imaging have used high spatial resolution techniques and have increasingly been performed to screen a high-risk population as well as to evaluate the extent of disease. This work has shown that MR imaging is the most sensitive modality currently available for identifying DCIS and is more accurate than mammography in evaluating the extent of DCIS. MR imaging is particularly sensitive for identifying high-grade and intermediate-grade DCIS. DCIS may have variable morphologic features on MR images, with non-mass enhancement morphology being the most common manifestation. Less commonly, DCIS may also manifest as a mass on MR images, in which case it is most likely to be irregular. The kinetics of DCIS are also variable, with fast uptake and a plateau curve reported as the most common kinetic pattern. Additional MR imaging tools such as diffusion-weighted imaging and quantitative kinetic analysis combined with the benefit of high field strength, such as 3 T, may increase the sensitivity and specificity of breast MR imaging in the detection of DCIS. (c) RSNA, 2013.
PMID: 24108552
ISSN: 0271-5333
CID: 571422
A better characterization of spinal cord damage in multiple sclerosis: a diffusional kurtosis imaging study
Raz, E; Bester, M; Sigmund, E E; Tabesh, A; Babb, J S; Jaggi, H; Helpern, J; Mitnick, R J; Inglese, M
BACKGROUND AND PURPOSE: The spinal cord is a site of predilection for MS lesions. While diffusion tensor imaging is useful for the study of anisotropic systems such as WM tracts, it is of more limited utility in tissues with more isotropic microstructures (on the length scales studied with diffusion MR imaging) such as gray matter. In contrast, diffusional kurtosis imaging, which measures both Gaussian and non-Gaussian properties of water diffusion, provides more biomarkers of both anisotropic and isotropic structural changes. The aim of this study was to investigate the cervical spinal cord of patients with MS and to characterize lesional and normal-appearing gray matter and WM damage by using diffusional kurtosis imaging. MATERIALS AND METHODS: Nineteen patients (13 women, mean age = 41.1 +/- 10.7 years) and 16 controls (7 women, mean age = 35.6 +/- 11.2-years) underwent MR imaging of the cervical spinal cord on a 3T scanner (T2 TSE, T1 magnetization-prepared rapid acquisition of gradient echo, diffusional kurtosis imaging, T2 fast low-angle shot). Fractional anisotropy, mean diffusivity, and mean kurtosis were measured on the whole cord and in normal-appearing gray matter and WM. RESULTS: Spinal cord T2-hyperintense lesions were identified in 18 patients. Whole spinal cord fractional anisotropy and mean kurtosis (P = .0009, P = .003), WM fractional anisotropy (P = .01), and gray matter mean kurtosis (P = .006) were significantly decreased, and whole spinal cord mean diffusivity (P = .009) was increased in patients compared with controls. Mean spinal cord area was significantly lower in patients (P = .04). CONCLUSIONS: Diffusional kurtosis imaging of the spinal cord can provide a more comprehensive characterization of lesions and normal-appearing WM and gray matter damage in patients with MS. Diffusional kurtosis imaging can provide additional and complementary information to DTI on spinal cord pathology.
PMID: 23578677
ISSN: 0195-6108
CID: 528992
Renal Blood Oxygenation Level-Dependent Imaging: Contribution of R2 to R2* Values
Vivier, Pierre-Hugues; Storey, Pippa; Chandarana, Hersh; Yamamoto, Akira; Tantillo, Kristopher; Khan, Umer; Zhang, Jeff L; Sigmund, Eric E; Rusinek, Henry; Babb, James S; Bubenheim, Michael; Lee, Vivian S
OBJECTIVES: The aim of this study was to assess the impact of oral water and intravenous furosemide challenges on blood oxygenation level-dependent magnetic resonance imaging measurements in the kidney and to examine the contribution of R2 (=1/T2) to changes in R2* (=1/T2*). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant study had institutional review board approval, and written informed consent was obtained from all subjects. Nine healthy volunteers were imaged at 3 T on 2 visits. During each visit, a baseline fasting magnetic resonance acquisition was followed by a diuretic challenge: oral water load for the first visit and furosemide for the second. R2* and R2 values in the renal cortex and medulla were measured using multiple gradient echo and multiple spin echo sequences, respectively, and R2' values were computed as R2' = R2* - R2. Timed urinary output was also measured. RESULTS: Averaged across all subjects, the R2* response to furosemide was greater than to water and greater in the medulla than the cortex. The mean R2 responses exhibited the same trends but were uniformly smaller than the mean R2* responses. The peak changes in R2* and R2 appeared, on average, 10 to 14 minutes before peak urinary output. The median percentage contribution of R2 to R2* changes was 16% in the medulla after both challenges. In the cortex, the median contribution was 48% after water load and 58% after furosemide challenge. CONCLUSIONS: The contributions of R2 to R2* changes after water load and furosemide challenge are not negligible, especially in the renal cortex. In routine clinical practice, R2* could be used alone as a rough surrogate for R2' in the medulla. However, in the cortex, both R2 and R2* should be measured to obtain accurate values of R2'.
PMCID:5053024
PMID: 23385400
ISSN: 0020-9996
CID: 231582
Toward simultaneous PET/MR breast imaging: Systematic evaluation and integration of a radiofrequency breast coil
Aklan, Bassim; Paulus, Daniel H; Wenkel, Evelyn; Braun, Harald; Navalpakkam, Bharath K; Ziegler, Susanne; Geppert, Christian; Sigmund, Eric E; Melsaether, Amy; Quick, Harald H
Purpose: With the recent introduction of integrated whole-body hybrid positron emission tomography/magnetic resonance (PET/MR) scanners, simultaneous PET/MR breast imaging appears to be a potentially attractive new clinical application. In this study, the technical groundwork toward performing simultaneous PET/MR breast imaging was developed and systematically evaluated in phantom experiments and breast cancer patient hybrid imaging.Methods: Measurements were performed on a state-of-the-art whole-body simultaneous PET/MR system (Biograph mMR, Siemens AG, Erlangen, Germany). The PET signal attenuating effects of a MR-only four-channel radiofrequency (RF) breast coil that is present in the PET field-of-view (FoV) during a simultaneous PET/MR data acquisition has been investigated and quantified. For this purpose, a dedicated PET/MR visible breast phantom featuring four modular inserts with various structures (no insert, MR insert, PET insert, and PET/MR insert) was developed. In addition to a systematic evaluation of MR-only image quality, the following phantom scans were performed using (18)F radio tracer: (1) PET emission scan with only the homogeneous breast phantom; (2) PET emission scan additionally with the RF breast coil in the PET FoV. Attenuation correction (AC) of PET data was performed with CT-based three-dimensional (3D) hardware attenuation maps (mu-maps) of the RF coil and breast phantom. Finally, a simultaneous PET/MR breast imaging was performed in two breast cancer patients.Results: The modular breast phantom allowed for systematic evaluation of various MR, PET, and PET/MR image quality parameters. The RF breast coil provided MR images of good image quality, unaffected by PET imaging. The global attenuation of the RF breast coil on the PET emission data was approximately 11%. This hardware attributed PET signal attenuation was successfully corrected by using an appropriate CT-based 3D mu-map of the RF breast coil. Imaging of two breast cancer patients confirmed the successful integration of the RF breast coil into the concept of simultaneous PET/MR breast imaging.Conclusions: The successful integration of a four-channel RF breast coil with a defined table position together with the CT-based mu-maps provides a technical basis for future clinical PET/MR breast imaging applications.
PMID: 23387782
ISSN: 0094-2405
CID: 231652
Assessment of hepatocellular carcinoma using apparent diffusion coefficient and diffusion kurtosis indices: preliminary experience in fresh liver explants
Rosenkrantz, Andrew B; Sigmund, Eric E; Winnick, Aaron; Niver, Benjamin E; Spieler, Bradley; Morgan, Glyn R; Hajdu, Cristina H
OBJECTIVES: The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants. METHODS: Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm(2). A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity. RESULTS: The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P=.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P=.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=-0.80), a weaker inverse correlation with D (-0.24) and a direct correlation with K (r=0.48). CONCLUSIONS: We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging.
PMID: 22819175
ISSN: 0730-725x
CID: 180402