Simultaneous whole-liver water T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ mapping with isotropic resolution during free-breathing.

PURPOSE: To develop and validate a data acquisition scheme combined with a motion-resolved reconstruction and dictionary-matching-based parameter estimation to enable free-breathing isotropic resolution self-navigated whole-liver simultaneous water-specific T 1 $$ {\mathrm{T}}_1 $$ ( wT 1 $$ {\mathrm{wT}}_1 $$ ) and T 2 $$ {\mathrm{T}}_2 $$ ( wT 2 $$ {\mathrm{wT}}_2 $$ ) mapping for the characterization of diffuse and oncological liver diseases. METHODS: The proposed data acquisition consists of a magnetization preparation pulse and a two-echo gradient echo readout with a radial stack-of-stars trajectory, repeated with different preparations to achieve different T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ contrasts in a fixed acquisition time of 6 min. Regularized reconstruction was performed using self-navigation to account for motion during the free-breathing acquisition, followed by water-fat separation. Bloch simulations of the sequence were applied to optimize the sequence timing for B 1 $$ {B}_1 $$ insensitivity at 3 T, to correct for relaxation-induced blurring, and to map T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ using a dictionary. The proposed method was validated on a water-fat phantom with varying relaxation properties and in 10 volunteers against imaging and spectroscopy reference values. The performance and robustness of the proposed method were evaluated in five patients with abdominal pathologies. RESULTS: Simulations demonstrate good B 1 $$ {B}_1 $$ insensitivity of the proposed method in measuring T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ values. The proposed method produces co-registered wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ maps with a good agreement with reference methods (phantom: wT 1 = 1 . 02 wT 1,ref - 8 . 93 ms , R 2 = 0 . 991 $$ {\mathrm{wT}}_1=1.02\kern0.1em {\mathrm{wT}}_{1,\mathrm{ref}}-8.93\kern0.1em \mathrm{ms},{R}^2=0.991 $$ ; wT 2 = 1 . 03 wT 2,ref + 0 . 73 ms , R 2 = 0 . 995 $$ {\mathrm{wT}}_2=1.03\kern0.1em {\mathrm{wT}}_{2,\mathrm{ref}}+0.73\kern0.1em \mathrm{ms},{R}^2=0.995 $$ ). The proposed wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ mapping exhibits good repeatability and can be robustly performed in patients with pathologies. CONCLUSIONS: The proposed method allows whole-liver wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ quantification with high accuracy at isotropic resolution in a fixed acquisition time during free-breathing.

Thoracic aorta diameters in Marfan patients: Intraindividual comparison of 3D modified relaxation-enhanced angiography without contrast and triggering (REACT) with transthoracic echocardiography.

OBJECTIVE: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients. MATERIAL AND METHODS: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods. RESULTS: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate. CONCLUSIONS: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients.

Intermodal correlation of quantitative CT-data and MRI-biomarkers derived from synchronous spectral CT-maps and breast MRI-examinations with molecular biomarkers in invasive ductal breast carcinomas.

OBJECTIVE: To asses the correlation of data derived from dual-layer (DL)-CT material-maps and breast MRI data with molecular biomarkers in invasive breast carcinomas. METHODS: All patients at the University Breast Cancer Center who underwent a clinically indicated DLCT-scan and a breast MRI for staging of invasive ductal breast cancer from 2016 to 2020 were prospectively included. Iodine concentration-maps, and Zeffective-maps were reconstructed from the CT-datasets. T1w- and T2w-signal intensities, ADC and the clustered shapes of the dynamic-curves (washout, plateau, persistent) were derived from the MRI-datasets. ROI-based evaluations of the cancers and the reference "musculature" were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearmans rank correlation and (multivariable) partial correlation. RESULTS: The signal intensities measured in the 3rd phase of the contrast dynamics correlated at an intermediate level of significance with the iodine content and the Zeffective-values derived from the breast target lesions (Spearmans rank correlation-coefficient r = 0.237/0.236, p = 0.002/0.003). The bivariate and the multivariate analyses displayed correlations of an intermediate significance level of the iodine content and the Zeff-values measured in the breast target lesions with immunhistochemical subtyping (r = 0.211-0.243, p = 0.002-0.009, respectively). The Zeff-values showed the strongest correlations when normalized to the values measured in the musculature and in the aorta (r = -0.237 to -0.305, r=<0.001-0.003). The MRI-assessments showed correlations of intermediate to high significance and low to intermediate significance between the ratios of the T2w-signal intensities and the trends of the dynamic curves measured in the breast target lesions and in musculature and immunohistochemical cancer subtyping, respectively (T2w: r = 0.232-0.249, p = 0.003/0.002; dynamics: r = -0.322/-0.245, p=<0.001/0.002). The ratios of the clustered trends of the dynamic curves measured in the breast target lesions and in musculature correlated with tumor grading on intermediate significance level (r = -0.213 and -0.194, p = 0.007/0.016) and with Ki-67 on a low significance level (bivariate analysis: r = -0.160, p = 0.040). There was only a weak correlation between the ADC-values measured in the breast target lesions and HER2-expression (bivariate ansalysis: r = 0.191, p = 0.030). CONCLUSIONS: Our preliminary results indicate that evaluation of perfusion based DLCT-data and MRI-biomarkers show correlations with the immunhistochemical subtyping of invasive ductal breast carcinomas. Further clinical research is warranted in order to validate the value of the results and define clinical situations in which the use of the described DLCT-biomaker and MRI biomarkers may be helpful in clinical patient care.

Robust breast quantitative susceptibility mapping in the presence of silicone.

PURPOSE: To (a) develop a preconditioned water-fat-silicone total field inversion (wfsTFI) algorithm that directly estimates the susceptibility map from complex multi-echo data in the breast in the presence of silicone and to (b) evaluate the performance of wfsTFI for breast quantitative susceptibility mapping (QSM) in silico and in vivo in comparison with formerly proposed methods. METHODS: Numerical simulations and in vivo multi-echo gradient echo breast measurements were performed to compare wfsTFI to a previously proposed field map-based linear total field inversion algorithm (lTFI) with and without the consideration of the chemical shift of silicone in the field map estimation step. Specifically, a simulation based on an in vivo scan and data from five patients were included in the analysis. RESULTS: In the simulation, wfsTFI is able to significantly decrease the normalized root mean square error from lTFI without (4.46) and with (1.77) the consideration of the chemical shift of silicone to 0.68. Both the in silico and in vivo wfsTFI susceptibility maps show reduced shadowing artifacts in local tissue adjacent to silicone, reduced streaking artifacts and no erroneous single voxels of diamagnetic susceptibility in proximity to silicone. CONCLUSION: The proposed wfsTFI method can automatically distinguish between subjects with and without silicone. Furthermore wfsTFI accounts for the presence of silicone in the QSM dipole inversion and allows for the robust estimation of susceptibility in proximity to silicone breast implants and hence allows the visualization of structures that would otherwise be dominated by artifacts on susceptibility maps.

Computed high-b-value high-resolution DWI improves solid lesion detection in IPMN of the pancreas.

OBJECTIVES: To examine the effect of high-b-value computed diffusion-weighted imaging (cDWI) on solid lesion detection and classification in pancreatic intraductal papillary mucinous neoplasm (IPMN), using endoscopic ultrasound (EUS) and histopathology as a standard of reference. METHODS: Eighty-two patients with known or suspected IPMN were retrospectively enrolled. Computed high-b-value images at b = 1000 s/mm2 were calculated from standard (b = 0, 50, 300, and 600 s/mm2) DWI images for conventional full field-of-view (fFOV, 3 × 3 × 4 mm3 voxel size) DWI. A subset of 39 patients received additional high-resolution reduced-field-of-view (rFOV, 2.5 × 2.5 × 3 mm3 voxel size) DWI. In this cohort, rFOV cDWI was compared against fFOV cDWI additionally. Two experienced radiologists evaluated (Likert scale 1-4) image quality (overall image quality, lesion detection and delineation, fluid suppression within the lesion). In addition, quantitative image parameters (apparent signal-to-noise ratio (aSNR), apparent contrast-to-noise ratio (aCNR), contrast ratio (CR)) were assessed. Diagnostic confidence regarding the presence/absence of diffusion-restricted solid nodules was assessed in an additional reader study. RESULTS: High-b-value cDWI at b = 1000 s/mm2 outperformed acquired DWI at b = 600 s/mm2 regarding lesion detection, fluid suppression, aCNR, CR, and lesion classification (p = < .001-.002). Comparing cDWI from fFOV and rFOV revealed higher image quality in high-resolution rFOV-DWI compared to conventional fFOV-DWI (p ≤ .001-.018). High-b-value cDWI images were rated non-inferior to directly acquired high-b-value DWI images (p = .095-.655). CONCLUSIONS: High-b-value cDWI may improve the detection and classification of solid lesions in IPMN. Combining high-resolution imaging and high-b-value cDWI may further increase diagnostic precision. CLINICAL RELEVANCE STATEMENT: This study shows the potential of computed high-resolution high-sensitivity diffusion-weighted magnetic resonance imaging for solid lesion detection in pancreatic intraductal papillary mucinous neoplasia (IPMN). The technique may enable early cancer detection in patients under surveillance. KEY POINTS: • Computed high-b-value diffusion-weighted imaging (cDWI) may improve the detection and classification of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. • cDWI calculated from high-resolution imaging increases diagnostic precision compared to cDWI calculated from conventional-resolution imaging. • cDWI has the potential to strengthen the role of MRI for screening and surveillance of IPMN, particularly in view of the rising incidence of IPMNs combined with now more conservative therapeutic approaches.

Assessing breast density using the chemical-shift encoding-based proton density fat fraction in 3-T MRI.

OBJECTIVES: There is a clinical need for a non-ionizing, quantitative assessment of breast density, as one of the strongest independent risk factors for breast cancer. This study aims to establish proton density fat fraction (PDFF) as a quantitative biomarker for fat tissue concentration in breast MRI and correlate mean breast PDFF to mammography. METHODS: In this retrospective study, 193 women were routinely subjected to 3-T MRI using a six-echo chemical shift encoding-based water-fat sequence. Water-fat separation was based on a signal model accounting for a single T2* decay and a pre-calibrated 7-peak fat spectrum resulting in volumetric fat-only, water-only images, PDFF- and T2*-values. After semi-automated breast segmentation, PDFF and T2* values were determined for the entire breast and fibroglandular tissue. The mammographic and MRI-based breast density was classified by visual estimation using the American College of Radiology Breast Imaging Reporting and Data System categories (ACR A-D). RESULTS: The PDFF negatively correlated with mammographic and MRI breast density measurements (Spearman rho: -0.74, p < .001) and revealed a significant distinction between all four ACR categories. Mean T2* of the fibroglandular tissue correlated with increasing ACR categories (Spearman rho: 0.34, p < .001). The PDFF of the fibroglandular tissue showed a correlation with age (Pearson rho: 0.56, p = .03). CONCLUSION: The proposed breast PDFF as an automated tissue fat concentration measurement is comparable with mammographic breast density estimations. Therefore, it is a promising approach to an accurate, user-independent, and non-ionizing breast density assessment that could be easily incorporated into clinical routine breast MRI exams. KEY POINTS: • The proposed PDFF strongly negatively correlates with visually determined mammographic and MRI-based breast density estimations and therefore allows for an accurate, non-ionizing, and user-independent breast density measurement. • In combination with T2*, the PDFF can be used to track structural alterations in the composition of breast tissue for an individualized risk assessment for breast cancer.

Prospectively Accelerated T2-Weighted Imaging of the Prostate by Combining Compressed SENSE and Deep Learning in Patients with Histologically Proven Prostate Cancer.

BACKGROUND: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa). METHODS: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.4 and 4.8 in 10 healthy volunteers and 23 patients with histologically proven PCa. Image reconstructions using compressed SENSE (C-SENSE) and a combination of C-SENSE and DL-based artificial intelligence (C-SENSE AI) were analyzed. Qualitative image comparison was performed using a 6-point Likert scale (overall image quality, noise, motion artifacts, lesion detection, diagnostic certainty); the T2 and PI-RADS scores were compared between the two reconstructions. Additionally, quantitative image parameters were assessed (apparent SNR, apparent CNR, lesion size, line profiles). RESULTS: All C-SENSE AI-reconstructed images received a significantly higher qualitative rating compared to the C-SENSE standard images. Analysis of the quantitative parameters supported this finding, with significantly higher aSNR and aCNR. The line profiles demonstrated a significantly steeper signal change at the border of the prostatic lesion and the adjacent normal tissue in the C-SENSE AI-reconstructed images, whereas the T2 and PI-RADS scores as well as the lesion size did not differ. CONCLUSION: In this prospective study, we demonstrated the clinical feasibility of a novel C-SENSE AI reconstruction enabling a 58% acceleration in T2w imaging of the prostate while obtaining significantly better image quality.

Imaging of the extracranial internal carotid artery in acute ischemic stroke: assessment of stenosis, plaques, and image quality using relaxation-enhanced angiography without contrast and triggering (REACT).

Background: In stroke magnetic resonance imaging (MRI), contrast-enhanced magnetic resonance angiography (CE-MRA) is the clinical standard to depict extracranial arteries but native MRA techniques are of increased interest to facilitate clinical practice. The purpose of this study was to assess the detection of extracranial internal carotid artery (ICA) stenosis and plaques as well as the image quality of cervical carotid arteries between a novel flow-independent relaxation-enhanced angiography without contrast and triggering (REACT) sequence and CE-MRA in acute ischemic stroke (AIS). Methods: In this retrospective, single-center study, 105 consecutive patients (65.27±18.74 years, 63 males) were included, who received a standard stroke protocol at 3T in clinical routine including Compressed SENSE (CS) accelerated (factor 4) 3D isotropic REACT (fixed scan time: 02:46 min) and CS accelerated (factor 6) 3D isotropic CE-MRA. Three radiologists independently assessed scans for the presence of extracranial ICA stenosis and plaques (including hyper-/hypointense signal) with concomitant diagnostic confidence using 3-point scales (3= excellent). Vessel quality, artifacts, and image noise of extracranial carotid arteries were subjectively scored on 5-point scales (5= excellent/none). Wilcoxon tests were used for statistical comparison. Results: Considering CE-MRA as the standard of reference, REACT provided a sensitivity of 89.8% and specificity of 95.2% for any and of 93.5% and 95.8% for clinically relevant (≥50%) extracranial ICA stenosis and yielded a to CE-MRA comparable diagnostic confidence [mean ± standard deviation (SD), median (interquartile range): 2.8±0.5, 3 (3-3) vs. 2.7±0.5, 3 (2-3), P=0.03]. Using REACT, readers detected more plaques overall (n=57.3 vs. 47.7, P<0.001) and plaques of hyperintense signal (n=12.3 vs. 5.7, P=0.02) with higher diagnostic confidence [2.8±0.5, 3 (3-3) vs. 2.6±0.7, 3 (2-3), P<0.001] than CE-MRA. After analyzing a total of 1,260 segments, the vessel quality of all segments combined [4.61±0.66 vs. 4.58±0.68, 5 (4-5) vs. 5 (4-5), P=0.0299] and artifacts [4.51±0.70 vs. 4.44±0.73, 5 (4-5) vs. 5 (4-5), P>0.05] were comparable between the sequences with REACT showing a lower image noise [4.43±0.67 vs. 4.25±0.71, 5 (4-5) vs. 4 (4-5), P<0.001]. Conclusions: Without the use of gadolinium-based contrast agents or triggering, REACT provides a high sensitivity and specificity for extracranial ICA stenosis and a potential improved depiction of adjacent plaques while yielding to CE-MRA comparable vessel quality in a large patient cohort with AIS.

High-Resolution, High b-Value Computed Diffusion-Weighted Imaging Improves Detection of Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Our purpose was to investigate the potential of high-resolution, high b-value computed DWI (cDWI) in pancreatic ductal adenocarcinoma (PDAC) detection. MATERIALS AND METHODS: We retrospectively enrolled 44 patients with confirmed PDAC. Respiratory-triggered, diffusion-weighted, single-shot echo-planar imaging (ss-EPI) with both conventional (i.e., full field-of-view, 3 × 3 × 4 mm voxel size, b = 0, 50, 300, 600 s/mm2) and high-resolution (i.e., reduced field-of-view, 2.5 × 2.5 × 3 mm voxel size, b = 0, 50, 300, 600, 1000 s/mm2) imaging was performed for suspected PDAC. cDWI datasets at b = 1000 s/mm2 were generated for the conventional and high-resolution datasets. Three radiologists were asked to subjectively rate (on a Likert scale of 1-4) the following metrics: image quality, lesion detection and delineation, and lesion-to-pancreas intensity relation. Furthermore, the following quantitative image parameters were assessed: apparent signal-to-noise ratio (aSNR), contrast-to-noise ratio (aCNR), and lesion-to-pancreas contrast ratio (CR). RESULTS: High-resolution, high b-value computed DWI (r-cDWI1000) enabled significant improvement in lesion detection and a higher incidence of a high lesion-to-pancreas intensity relation (type 1, clear hyperintense) compared to conventional high b-value computed and high-resolution high b-value acquired DWI (f-cDWI1000 and r-aDWI1000, respectively). Image quality was rated inferior in the r-cDWI1000 datasets compared to r-aDWI1000. Furthermore, the aCNR and CR were higher in the r-cDWI1000 datasets than in f-cDWI1000 and r-aDWI1000. CONCLUSION: High-resolution, high b-value computed DWI provides significantly better visualization of PDAC compared to the conventional high b-value computed and high-resolution high b-value images acquired by DWI.

Noise reduction in diffusion weighted MRI of the pancreas using an L1-regularized iterative SENSE reconstruction.

OBJECTIVES: To prospectively evaluate an L1 regularized iterative SENSE reconstruction (L1-R SENSE) to eliminate band-like artifacts frequently seen with parallel imaging (SENSE) at high acceleration factors in high resolution diffusion weighted magnetic resonance imaging of the pancreas. METHODS: Fourteen patients with pancreatic ductal adenocarcinoma (PDAC) underwent respiratory triggered DWI ss-EPI at a resolution of 2.5 × 2.5 × 3 mm3 with uniform undersampling in the phase encoding direction (AP axis) with an acceleration factor of 4. Data were reconstructed using the standard SENSE reconstruction routine of the vendor and an iterative SENSE reconstruction employing L1 regularization after a wavelet sparsifying transformation (L1-R SENSE). Retrospective reconstruction of the data with a lower number of averages was performed using both reconstruction methods. Two radiologists independently assessed noise artifacts, anatomical details and image quality (IQ) subjectively with a 4-point scale. Apparent diffusion coefficient (ADC) and covariance (CV) of ADC estimated from images reconstructed at a different number of averages for PDAC and the normal pancreas were assessed. RESULTS: L1-R SENSE resulted in higher IQ and less noise artifacts than SENSE. Anatomical details were significantly higher for SENSE in one reader. Mean ADC of PDAC and normal pancreas were significantly higher for L1-R SENSE than SENSE. L1-R SENSE revealed lower CV of ADC for normal pancreas compared to SENSE, whereas no difference was noted for PDAC. CONCLUSION: Compared with traditional SENSE reconstruction, L1-R SENSE effectively reduces band-like noise and improves the robustness of the ADC estimation from acquisitions using single-shot DW-EPI of the pancreas.

Preconditioned water-fat total field inversion: Application to spine quantitative susceptibility mapping.

PURPOSE: To (a) develop a preconditioned water-fat total field inversion (wfTFI) algorithm that directly estimates the susceptibility map from complex multi-echo gradient echo data for water-fat regions and to (b) evaluate the performance of the proposed wfTFI quantitative susceptibility mapping (QSM) method in comparison with a local field inversion (LFI) method and a linear total field inversion (TFI) method in the spine. METHODS: Numerical simulations and in vivo spine multi-echo gradient echo measurements were performed to compare wfTFI to an algorithm based on disjoint background field removal (BFR) and LFI and to a formerly proposed TFI algorithm. The data from 1 healthy volunteer and 10 patients with metastatic bone disease were included in the analysis. Clinical routine computed tomography (CT) images were used as a reference standard to distinguish osteoblastic from osteolytic changes. The ability of the QSM methods to distinguish osteoblastic from osteolytic changes was evaluated. RESULTS: The proposed wfTFI method was able to decrease the normalized root mean square error compared to the LFI and TFI methods in the simulation. The in vivo wfTFI susceptibility maps showed reduced BFR artifacts, noise amplification, and streaking artifacts compared to the LFI and TFI maps. wfTFI provided a significantly higher diagnostic confidence in differentiating osteolytic and osteoblastic lesions in the spine compared to the LFI method (p = .012). CONCLUSION: The proposed wfTFI method can minimize BFR artifacts, noise amplification, and streaking artifacts in water-fat regions and can thus better differentiate between osteoblastic and osteolytic changes in patients with metastatic disease compared to LFI and the original TFI method.

Influence of aging and gadolinium exposure on T1, T2, and T2*-relaxation in healthy women with an increased risk of breast cancer with and without prior exposure to gadoterate meglumine at 3.0-T brain MR imaging.

OBJECTIVES: We examined the effects of aging and of gadolinium-based contrast agent (GBCA) exposure on MRI measurements in brain nuclei of healthy women. METHODS: This prospective, IRB-approved single-center case-control study enrolled 100 healthy participants of our high-risk screening center for hereditary breast cancer, who had received at least six doses of macrocyclic GBCA (exposed group) or were newly entering the program (GBCA-naïve group). The cutoff "at least six doses" was chosen to be able to include a sufficient number of highly exposed participants. All participants underwent unenhanced 3.0-T brain MRI including quantitative T1, T2, and R2* mapping and T1- and T2-weighted imaging. The relaxation times/signal intensities were derived from region of interest measurements in the brain nuclei performed by a radiologist and a neuroradiologist, both board certified. Statistical analysis was based on descriptive evaluations and uni-/multivariable analyses. RESULTS: The participants (exposed group: 49, control group: 51) were aged 42 ± 9 years. In a multivariable model, age had a clear impact on R2* (p < 0.001-0.012), T2 (p = 0.003-0.048), and T1 relaxation times/signal intensities (p < 0.004-0.046) for the majority of deep brain nuclei, mostly affecting the substantia nigra, globus pallidus (GP), nucleus ruber, thalamus, and dentate nucleus (DN). The effect of prior GBCA administration on T1 relaxation times was statistically significant for the DN, GP, and pons (p = 0.019-0.037). CONCLUSIONS: In a homogeneous group of young to middle-aged healthy females aging had an effect on T2 and R2* relaxation times and former GBCA applications influenced the measured T1 relaxation times. KEY POINTS: The quantitative T1, T2, and R2* relaxation times measured in women at high risk of developing breast cancer showed characteristic bandwidth for all brain nuclei examined at 3.0-T MRI. The effect of participant age had a comparatively strong impact on R2*, T2, and T1 relaxation times for the majority of brain nuclei examined. The effect of prior GBCA administrations on T1 relaxation times rates was comparatively less pronounced, yielding statistically significant results for the dentate nucleus, globus pallidus, and pons. Healthy women with and without previous GBCA-enhanced breast MRI exhibited age-related T2* and T2 relaxation alterations at 3.0 T-brain MRI. T1 relaxation alterations due to prior GBCA administration were comparatively less pronounced.

Cerebrospinal fluid pulse wave velocity measurements: In vitro and in vivo evaluation of a novel multiband cine phase-contrast MRI sequence.

PURPOSE: Intracranial and intraspinal compliance are parameters of interest in the diagnosis and prediction of treatment outcome in patients with normal pressure hydrocephalus and other forms of communicating hydrocephalus. A noninvasive method to estimate the spinal cerebrospinal fluid (CSF) pulse wave velocity (PWV) as a measure of compliance was developed using a multiband cine phase-contrast MRI sequence and a foot-to-foot algorithm. METHODS: We used computational simulations to estimate the accuracy of the MRI acquisition and transit-time algorithm. In vitro measurements were performed to investigate the reproducibility and accuracy of the measurements under controlled conditions. In vivo measurements in 20 healthy subjects and 2 patients with normal pressure hydrocephalus were acquired to show the technical feasibility in a clinical setting. RESULTS: Simulations showed a mean deviation of the calculated CSF PWV of 3.41% ± 2.68%. In vitro results were in line with theory, showing a square-root relation between PWV and transmural pressure and a good reproducibility with SDs of repeated measurements below 5%. Mean CSF PWV over all healthy subjects was 5.83 ± 3.36 m/s. The CSF PWV measurements in the patients with normal pressure hydrocephalus were distinctly higher before CSF shunt surgery (33.80 ± 6.75 m/s and 31.31 ± 7.82 m/s), with a decrease 5 days after CSF shunt surgery (15.69 ± 3.37 m/s). CONCLUSION: This study evaluates the feasibility of CSF PWV measurements using a multiband cine phase-contrast MRI sequence. In vitro and in vivo measurements showed that this method is a potential tool for the noninvasive estimation of intraspinal compliance.

Compressed-sensing accelerated 4D flow MRI of cerebrospinal fluid dynamics.

BACKGROUND: 4D flow magnetic resonance imaging (MRI) of CSF can make an important contribution to the understanding of hydrodynamic changes in various neurological diseases but remains limited in clinical application due to long acquisition times. The aim of this study was to evaluate the accuracy of compressed SENSE accelerated MRI measurements of the spinal CSF flow. METHODS: In 20 healthy subjects 4D flow MRI of the CSF in the cervical spine was acquired using compressed sensitivity encoding [CSE, a combination of compressed sensing and parallel imaging (SENSE) provided by the manufacturer] with acceleration factors between 4 and 10. A conventional scan using SENSE was used as reference. Extracted parameters were peak velocity, absolute net flow, forward flow and backward flow. Bland-Altman analysis was performed to determine the scan-rescan reproducibility and the agreement between SENSE and compressed SENSE. Additionally, a time accumulated flow error was calculated. In one additional subject flow of the spinal canal at the level of the entire spinal cord was assessed. RESULTS: Averaged acquisition times were 10:21 min (SENSE), 9:31 min (CSE4), 6:25 min (CSE6), 4:53 min (CSE8) and 3:51 min (CSE10). Acquisition of the CSF flow surrounding the entire spinal cord took 14:40 min. Bland-Altman analysis showed good agreement for peak velocity, but slight overestimations for absolute net flow, forward flow and backward flow (< 1 ml/min) in CSE4-8. Results of the accumulated flow error were similar for CSE4 to CSE8. CONCLUSION: A quantitative analysis of acceleration factors CSE4-10 showed that CSE with an acceleration factor up to 6 is feasible. This allows a scan time reduction of 40% and enables the acquisition and analysis of the CSF flow dynamics surrounding the entire spinal cord within a clinically acceptable scan time.

Magnetic Resonance Kidney Parenchyma-T2 as a Novel Imaging Biomarker for Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is a chronic progressive disorder with a significant disease burden leading to end-stage renal disease in more than 75% of the affected individuals. Although prediction of disease progression is highly important, all currently available biomarkers-including height-adjusted total kidney volume (htTKV)-have important drawbacks in the everyday clinical setting. Thus, the purpose of this study was to evaluate T2 mapping as a source of easily obtainable and accurate biomarkers, which are needed for improved patient counseling and selection of targeted treatment options. MATERIALS AND METHODS: A total of 139 ADPKD patients from The German ADPKD Tolvaptan Treatment Registry and 10 healthy controls underwent magnetic resonance imaging on a clinical 1.5-T system including acquisition of a Gradient-Echo-Spin-Echo T2 mapping sequence. The ADPKD patients were divided into 3 groups according to kidney cyst fraction (0%-35%, 36%-70%, >70%) as a surrogate marker for disease severity. The htTKV was calculated based on standard T2-weighted imaging. Mean T2 relaxation times of both kidneys (kidney-T2) as well as T2 relaxation times of the residual kidney parenchyma (parenchyma-T2) were measured on the T2 maps. RESULTS: Calculation of parenchyma-T2 was 6- to 10-fold faster than determination of htTKV and kidney-T2 (0.78 ± 0.14 vs 4.78 ± 1.17 minutes, P < 0.001; 0.78 ± 0.14 vs 7.59 ± 1.57 minutes, P < 0.001). Parenchyma-T2 showed a similarly strong correlation to cyst fraction (r = 0.77, P < 0.001) as kidney-T2 (r = 0.76, P < 0.001), the strongest correlation to the serum-derived biomarker copeptin (r = 0.37, P < 0.001), and allowed for the most distinct separation of patient groups divided according to cyst fraction. In contrast, htTKV showed an only moderate correlation to cyst fraction (r = 0.48, P < 0.001). These observations were even more evident when considering only patients with preserved kidney function. CONCLUSIONS: The rapidly assessable parenchyma-T2 shows a strong association with disease severity early in disease and is superior to htTKV when it comes to correlation with renal cyst fraction.

Accelerated Clustered Sparse Acquisition to Improve Functional MRI for Mapping Language Functions.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a useful method for noninvasive presurgical functional mapping. However, the scanner environment is inherently unsuitable for the examination of auditory and language functions, due to the loud acoustic noise produced by the scanner. Interleaved acquisition methods alleviate this problem by providing a silent period for stimulus presentation and/or response control (sparse sampling) but at the expense of a diminished amount of data collected. There are possible improvements to these sparse acquisition methods that increase the amount of data by acquiring several images per event (clustered sampling). We tested accelerated clustered fMRI acquisition in comparison with conventional sparse sampling in a pilot study. METHODS: The clustered and sparse acquisition techniques (7.4 minutes scanning time per protocol) were directly compared in 15 healthy subjects (8 men; mean age: 24 ± 3 years) using both a motor (tongue movement) and a language (overt picture-naming) task. Functional imaging data were analyzed using Statistical Parametric Mapping software (SPM12 Wellcome Department of Imaging Neuroscience, London, UK). For both tasks, activation levels were compared and Euclidean distances (EDs) between cluster centers (i.e., local activation maxima and centers of gravity) were calculated. Overlaps and laterality indices were computed for the picture-naming task. In addition, the feasibility of the clustered acquisition protocol in a clinical setting was assessed in one pilot patient. RESULTS: For both tasks, activation levels were higher using the clustered acquisition protocol, reflected by bigger cluster sizes (p < 0.05). Mean ED between cluster centers ranged between 9.9 ± 5.4 mm (left superior temporal gyrus; centers of gravity) and 16.6 ± 13.2 mm (left inferior frontal gyrus; local activation maxima) for the picture-naming task. Overlaps between sparse and clustered acquisition reached 88% (Simpson overlap coefficient). A similar activation pattern for both acquisition methods was also confirmed in the clinical case. CONCLUSION: Despite some drawbacks inherent to the acquisition technique, the clustered sparse sampling protocol showed increased sensitivity for activation in language-related cortical regions with short scanning times. Such scanning techniques may be particularly advantageous for investigating patients with contraindications for long scans (e.g., reduced attention span).

Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in Heart Failure.

BACKGROUND: Among central and peripheral factors contributing to exercise intolerance (EI) in heart failure (HF), the extent to which skeletal muscle (SM) energy metabolic abnormalities occur and contribute to EI and increased fatigability in HF patients with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively) are not known. An energetic plantar flexion exercise fatigability test and magnetic resonance spectroscopy were used to probe the mechanistic in vivo relationships among SM high-energy phosphate concentrations, mitochondrial function, and EI in HFrEF and HFpEF patients and in healthy controls. METHODS AND RESULTS: Resting SM high-energy phosphate concentrations and ATP flux rates were normal in HFrEF and HFpEF patients. Fatigue occurred at similar SM energetic levels in all subjects, consistent with a common SM energetic limit. Importantly, HFrEF New York Heart Association class II-III patients with EI and high fatigability exhibited significantly faster rates of exercise-induced high-energy phosphate decline than did HFrEF patients with low fatigability (New York Heart Association class I), despite similar left ventricular ejection fractions. HFpEF patients exhibited severe EI, the most rapid rates of high-energy phosphate depletion during exercise, and impaired maximal oxidative capacity. CONCLUSIONS: Symptomatic fatigue during plantar flexion exercise occurs at a common energetic limit in all subjects. HFrEF and HFpEF patients with EI and increased fatigability manifest early, rapid exercise-induced declines in SM high-energy phosphates and reduced oxidative capacity compared with healthy and low-fatigability HF patients, suggesting that SM metabolism is a potentially important target for future HF treatment strategies.

Hyperpolarized Metabolic MR Imaging of Acute Myocardial Changes and Recovery after Ischemia-Reperfusion in a Small-Animal Model.

PURPOSE: To implement hyperpolarized magnetic resonance (MR) imaging in an animal model of ischemia-reperfusion and to assess in vivo the regional changes in pyruvate metabolism within the 1st hour and at 1 week after a brief episode of coronary occlusion and reperfusion. MATERIALS AND METHODS: All animal experiments were performed with adherence to the Swiss Animal Protection law and were approved by the regional veterinary office. A closed-chest rat model was implemented by using an inflatable balloon secured around the left coronary artery. Animals were placed in an MR system 5-7 days after surgery. [1-(13)C]pyruvate was polarized by using a home-built multisample hyperpolarizer. Hyperpolarized pyruvate was injected at five stages: at baseline; at reperfusion after 15 minutes of coronary occlusion; and at 30 minutes, 60 minutes, and 1 week after ischemia reperfusion. The conversion of pyruvate into lactate and bicarbonate was imaged by using dedicated MR sequences alongside wall motion and delayed enhancement imaging. After imaging, the heart was removed and stained to delineate the area at risk (AAR). Differences between AAR and remote myocardium were assessed by using a repeated measures analysis of variance and a post hoc Bonferroni multiple comparison test. RESULTS: Data were collected in 12 animals. Occlusion led to hypokinesia of the anterior or anterolateral segments of the myocardium. At reperfusion, the average lactate-to-bicarbonate ratio increased in the AAR relative to that at baseline (from 1.93 ± 0.48 to 3.01 ± 0.74, P < .001) and was significantly higher when compared with that in the remote area (1.91 ± 0.38, P < .001). In the 60 minutes after occlusion, the lactate-to-bicarbonate ratio in the AAR recovered but was still elevated relative to that in the remote area. One week after ischemia-reperfusion, no difference between AAR and remote area could be detected. CONCLUSION: Hyperpolarized metabolic MR imaging can be used to successfully detect acute changes in [1-(13)C]pyruvate metabolism after ischemia-reperfusion, thereby enabling in vivo monitoring of the metabolic effects of reperfusion strategies.

On the theoretical limits of detecting cyclic changes in cardiac high-energy phosphates and creatine kinase reaction kinetics using in vivo ³¹P MRS.

Adenosine triphosphate (ATP) is absolutely required to fuel normal cyclic contractions of the heart. The creatine kinase (CK) reaction is a major energy reserve reaction that rapidly converts creatine phosphate (PCr) to ATP during the cardiac cycle and at times of stress and ischemia, but is significantly impaired in conditions such as hypertrophy and heart failure. Because the magnitudes of possible in vivo cyclic changes in cardiac high-energy phosphates (HEPs) during the cardiac cycle are not well known from previous work, this study uses mathematical modeling to assess whether, and to what extent, cyclic variations in HEPs and in the rate of ATP synthesis through CK (CK flux) could exist in the human heart, and whether they could be measured with current in vivo (31)P MRS methods. Multi-site exchange models incorporating enzymatic rate equations were used to study the cyclic dynamics of the CK reaction, and Bloch equations were used to simulate (31)P MRS saturation transfer measurements of the CK reaction. The simulations show that short-term buffering of ATP by CK requires temporal variations over the cardiac cycle in the CK reaction velocities modeled by enzymatic rate equations. The maximum variation in HEPs in the normal human heart beating at 60 min(-1) was approximately 0.4 mM and proportional to the velocity of ATP hydrolysis. Such HEP variations are at or below the current limits of detection by in vivo (31)P MRS methods. Bloch equation simulations show that (31)P MRS saturation transfer estimates the time-averaged, pseudo-first-order forward rate constant, k(f,ap)', of the CK reaction, and that periodic short-term fluctuations in kf ' and CK flux are not likely to be detectable in human studies employing current in vivo (31)P MRS methods.