Purpose: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm... Show morePurpose: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. Methods: A 2D self-refocused T-2*-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp*T-chirp) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q similar to 75 encodes with the same off-resonance robustness as EPI. Results: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately similar to 85 and similar to 108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than similar to 1000 ms. Conclusion: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning. Show less
Introduction: Health systems worldwide face the challenge of increasing population health with high-quality care and reducing health care expenditure growth. In pursuit for a solution, regional... Show moreIntroduction: Health systems worldwide face the challenge of increasing population health with high-quality care and reducing health care expenditure growth. In pursuit for a solution, regional cross-sectoral partnerships aim to reorganize and integrate services across public health, health care and social care. Although the complexity of regional partnerships demands an incremental strategy, it is yet not known how learning works within these partnerships. To understand learning in regional cross-sectoral partnerships for health, this study aims to map the concept Learning Health System (LHS). Methods: This mapping review used a qualitative text analysis approach. A literature search was conducted in Embase and was limited to English-language papers published in the period 2015-2020. Title-abstract screening was performed using established exclusion criteria. During full-text screening, we combined deductive and inductive coding. The concept LHS was disentangled into aims, design elements, and process of learning. Data extraction and analysis were performed in MAX QDA 2020. Results: In total, 155 articles were included. All articles used the LHS definition of the Institute of Medicine. The interpretation of the concept LHS varied widely. The description of LHS contained 25 highly connected aims. In addition, we identified nine design elements. Most elements were described similarly, only the interpretation of stakeholders, data infrastructure and data varied. Furthermore, we identified three types of learning: learning as 1) interaction between clinical practice and research; 2) a circular process of converting routine care data to knowledge, knowledge to performance; and performance to data; and 3) recurrent interaction between stakeholders to identify opportunities for change, to reveal underlying values, and to evaluate processes. Typology 3 was underrepresented, and the three types of learning rarely occurred simultaneously. Conclusion: To understand learning within regional cross-sectorat partnerships for health, we suggest to specify LHS-aim(s), operationalize design elements, and choose deliberately appropriate learning type(s). Show less
IntroductionHealth systems worldwide face the challenge of increasing population health with high-quality care and reducing health care expenditure growth. In pursuit for a solution, regional cross... Show moreIntroductionHealth systems worldwide face the challenge of increasing population health with high-quality care and reducing health care expenditure growth. In pursuit for a solution, regional cross-sectoral partnerships aim to reorganize and integrate services across public health, health care and social care. Although the complexity of regional partnerships demands an incremental strategy, it is yet not known how learning works within these partnerships. To understand learning in regional cross-sectoral partnerships for health, this study aims to map the concept Learning Health System (LHS).MethodsThis mapping review used a qualitative text analysis approach. A literature search was conducted in Embase and was limited to English-language papers published in the period 2015-2020. Title-abstract screening was performed using established exclusion criteria. During full-text screening, we combined deductive and inductive coding. The concept LHS was disentangled into aims, design elements, and process of learning. Data extraction and analysis were performed in MAX QDA 2020.ResultsIn total, 155 articles were included. All articles used the LHS definition of the Institute of Medicine. The interpretation of the concept LHS varied widely. The description of LHS contained 25 highly connected aims. In addition, we identified nine design elements. Most elements were described similarly, only the interpretation of stakeholders, data infrastructure and data varied. Furthermore, we identified three types of learning: learning as 1) interaction between clinical practice and research; 2) a circular process of converting routine care data to knowledge, knowledge to performance; and performance to data; and 3) recurrent interaction between stakeholders to identify opportunities for change, to reveal underlying values, and to evaluate processes. Typology 3 was underrepresented, and the three types of learning rarely occurred simultaneously.ConclusionTo understand learning within regional cross-sectoral partnerships for health, we suggest to specify LHS-aim(s), operationalize design elements, and choose deliberately appropriate learning type(s). Show less
Oost, L.J.; Heijden, A.A.W.A. van der; Vermeulen, E.A.; Bos, C.; Elders, P.J.M.; Slieker, R.C.; ... ; Baaij, J.H.F. de 2021
OBJECTIVE We investigated whether serum magnesium (Mg2+) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (hemoglobin A(1c) [HbA(1c)]), in... Show moreOBJECTIVE We investigated whether serum magnesium (Mg2+) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (hemoglobin A(1c) [HbA(1c)]), in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We analyzed in 4,348 participants the association of serum Mg2+ with macrovascular disease and mortality (acute myocardial infarction [AMI], coronary heart disease [CHD], heart failure [HF], cerebrovascular accident [CVA], and peripheral arterial disease [PAD]), atrial fibrillation (AF), and microvascular complications (chronic kidney disease [CKD], diabetic retinopathy, and diabetic foot) using Cox regression, adjusted for confounders. Mediation analysis was performed to assess whether HbA(1c) mediated these associations. RESULTS The average baseline serum Mg2+ concentration was 0.80 +/- 0.08 mmol/L. During 6.1 years of follow-up, serum Mg2+ was inversely associated with major macrovascular, 0.87 (95% CI 0.76; 1.00); HF, 0.76 (95% CI 0.62; 0.93); and AF, 0.59 (95% CI 0.49; 0.72). Serum Mg2+ was not associated with AMI, CHD, CVA, and PAD. During 5.1 years of follow-up, serum Mg2+ was inversely associated with overall microvascular events, 0.85 (95% CI 0.78; 0.91); 0.89 (95% CI 0.82; 0.96) for CKD, 0.77 (95% CI 0.61; 0.98) for diabetic retinopathy, and 0.85 (95% CI 0.78; 0.92) for diabetic foot. HbA(1c) mediated the associations of serum Mg2+ with HF, overall microvascular events, diabetic retinopathy, and diabetic foot. CONCLUSIONS Serum Mg2+ concentration is inversely associated with the risk to develop HF and AF and with the occurrence of CKD, diabetic retinopathy, and foot complications in T2D. Glycemic control partially mediated the association of serum Mg2+ with HF and microvascular complications. Show less
Background Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based... Show moreBackground Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable.Purpose To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue.Study Type Prospective.Population Eight breast cancer patients.Field Strength/Sequence A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout.Assessment VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam.Statistical Tests Intra-class correlation coefficient (ICC) for interobserver agreement.Results The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score.Data Conclusion We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients.Evidence Level 1Technical Efficacy Stage 1 Show less
Purpose Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In... Show morePurpose Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR).Methods Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior-posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported.Results In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was <= 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 +/- 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 +/- 84 mL/min/100 g) and 10 cm/s (472 +/- 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 +/- 84 mL/min/100 g) (P > .05) with good correlations on subject level.Conclusion Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR. Show less
Franklin, S.L.; Bones, I.K.; Harteveld, A.A.; Hirschler, L.; Stralen, M. van; Qin, Q.; ... ; Schmid, S. 2020
Purpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which... Show morePurpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]).Methods Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney).Results In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B-1-inhomogeneity. All ASL techniques were relatively robust to respiratory motion.Conclusion In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B-1-sensitivity of VSI-ASL is necessary to match the performance of FAIR. Show less
Boer, A. de; Harteveld, A.A.; Stemkens, B.; Blankestijn, P.J.; Bos, C.; Franklin, S.L.; ... ; Leiner, T. 2020
Background: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.Purpose: To determine intrasubject test... Show moreBackground: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.Purpose: To determine intrasubject test-retest repeatability of renal MRI measurements.Study Type: Prospective.Population: Nineteen healthy subjects aged over 40 years.Field Strength/Sequences: T-1 and T-2 mapping, R-2* mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T.Assessment: Subjects were scanned twice with similar to 1 week between visits. Total scan time was similar to 1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model. Statistical Test: To assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated.Results: CoVs for relaxometry (T-1, T-2, R-2*/BOLD) were below 6.1%, with the lowest CoVs for T-2 maps and highest for R-2*/BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP, respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively).Data Conclusion: CoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology. Show less
Purpose Arterial transit time uncertainties and challenges during planning are potential issues for renal perfusion measurement using spatially selective arterial spin labeling techniques. To... Show morePurpose Arterial transit time uncertainties and challenges during planning are potential issues for renal perfusion measurement using spatially selective arterial spin labeling techniques. To mitigate these potential issues, a spatially non-selective technique, such as velocity-selective arterial spin labeling (VSASL), could be an alternative. This article explores the influence of VSASL sequence parameters and respiratory induced motion on VS-label generation. Methods VSASL data were acquired in human subjects (n= 15), with both single and dual labeling, during paced-breathing, while essential sequence parameters were systematically varied; (1) cutoff velocity, (2) labeling gradient orientation and (3) post-labeling delay (PLD). Pseudo-continuous ASL was acquired as a spatially selective reference. In an additional free-breathing single VSASL experiment (n= 9) we investigated respiratory motion influence on VS-labeling. Absolute renal blood flow (RBF), perfusion weighted signal (PWS), and temporal signal-to-noise ratio (tSNR) were determined. Results (1) With decreasing cutoff velocity, tSNR and PWS increased. However, undesired tissue labeling occurred at low cutoff velocities (<= 5.4 cm/s). (2) Labeling gradient orientation had little effect on tSNR and PWS. (3) For single VSASL high signal appeared in the kidney pedicle at PLD < 800 ms, and tSNR and PWS decreased with increasing PLD. For dual VSASL, maximum tSNR occurred at PLD = 1200 ms. Average cortical RBF measured with dual VSASL (264 +/- 34 mL/min/100 g) at a cutoff velocity of 5.4 cm/s, and feet-head labeling was slightly lower than with pseudo-continuous ASL (283 +/- 55 mL/min/100 g). Conclusion With well-chosen sequence parameters, tissue labeling induced by respiratory motion can be minimized, allowing to obtain good quality RBF maps using planning-free labeling with dual VSASL. Show less
Harteveld, A.A.; Hutter, J.; Franklin, S.L.; Jackson, L.H.; Rutherford, M.; Hajnal, J.V.; ... ; Vita, E. de 2020
Purpose: Placental function is key for successful human pregnancies. Perfusion may be a sensitive marker for the in vivo assessment of placental function. Arterial spin labeling (ASL) MRI enables... Show morePurpose: Placental function is key for successful human pregnancies. Perfusion may be a sensitive marker for the in vivo assessment of placental function. Arterial spin labeling (ASL) MRI enables noninvasive measurement of tissue perfusion and it was recently suggested that ASL with velocity-selective (VS) labeling could be advantageous in the placenta. We systematically evaluated essential VS-ASL sequence parameters to determine optimal settings for efficient placental perfusion measurements.Methods: Eleven pregnant women were scanned at 3T using VS-ASL with 2D multislice echo planar imaging (EPI)-readout. One reference VS-ASL scan was acquired in all subjects; within subgroups the following parameters were systematically varied: cutoff velocity, velocity encoding direction, and inflow time. Visual evaluation and region of interest analyses were performed to compare perfusion signal differences between acquisitions.Results: In all subjects, a perfusion pattern with clear hyperintense focal regions was observed. Perfusion signal decreased with inflow time and cutoff velocity. Subject-specific dependence on velocity encoding direction was observed. High temporal signal-to-noise ratios with high contrast on the perfusion images between the hyperintense regions and placental tissue were seen at similar to 1.6 cm/s cutoff velocity and similar to 1000 ms inflow time. Evaluation of measurements at multiple inflow times revealed differences in blood flow dynamics between placental regions.Conclusion: Placental perfusion measurements are feasible at 3T using VS-ASL with 2D multislice EPI-readout. A clear dependence of perfusion signal on VS labeling parameters and inflow time was demonstrated. Whereas multiple parameter combinations may advance the interpretation of placental circulation dynamics, this study provides a basis to select an effective set of parameters for the observation of placenta perfusion natural history and its potential pathological changes. Show less
Franklin, S.L.; Schmid, S.; Bos, C.; Osch, M.J.P. van 2020
Purpose: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was... Show morePurpose: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was investigated.Methods: A short-PLD sequence was developed where a single VSASL- or AccASL-module was preceded by pCASL labeling to isolate the arterial blood pool. ASL subtraction was performed with label/control images with similar cardiac phase and time-of-measurement, followed by retrospective binning in 10 cardiac phase bins. ASL signal variation over the heart cycle was evaluated and tested for significance using a permutation test.Results: VSASL and AccASL showed significant arterial signal fluctuations over the cardiac cycle of up to similar to 36% and similar to 64%, respectively, mainly in areas containing large arteries. pCASL also showed significant signal fluctuations, of up to similar to 25% in arteries. Raw label/control images confirmed that the observed signal fluctuations were caused by the amount of label produced during the cardiac cycle, rather than inflow-effects, because the raw images did not all show equal cardiac phase dependence. No significant effects of the cardiac cycle were found on the gray matter ASL-signal.Conclusion: Significant influence of the cardiac cycle on the generated label was found for spatially nonselective ASL-sequences. Hence, to become independent of the cardiac cycle, sufficient averages need to be taken. Alternatively, these findings could be highly interesting for the purpose of quantifying pulsatility more distally in the vascular tree. Show less
Harteveld, A.A.; Boer, A. de; Franklin, S.L.; Leiner, T.; Stralen, M. van; Bos, C. 2020
Objective To compare the most commonly used labeling approaches, flow-sensitive alternating inversion recovery (FAIR) and pseudocontinuous arterial spin labeling (pCASL), for renal perfusion... Show moreObjective To compare the most commonly used labeling approaches, flow-sensitive alternating inversion recovery (FAIR) and pseudocontinuous arterial spin labeling (pCASL), for renal perfusion measurement using arterial spin labeling (ASL) MRI. Methods Multi-delay FAIR and pCASL were performed in 16 middle-aged healthy volunteers on two different occasions at 3T. Relative perfusion-weighted signal (PWS), temporal SNR (tSNR), renal blood flow (RBF), and arterial transit time (ATT) were calculated for the cortex and medulla in both kidneys. Bland-Altman plots, intra-class correlation coefficient, and within-subject coefficient of variation were used to assess reliability and agreement between measurements. Results For the first visit, RBF was 362 +/- 57 and 140 +/- 47 mL/min/100 g, and ATT was 0.47 +/- 0.13 and 0.70 +/- 0.10 s in cortex and medulla, respectively, using FAIR; RBF was 201 +/- 72 and 84 +/- 27 mL/min/100 g, and ATT was 0.71 +/- 0.25 and 0.86 +/- 0.12 s in cortex and medulla, respectively, using pCASL. For both labeling approaches, RBF and ATT values were not significantly different between visits. Overall, FAIR showed higher PWS and tSNR. Moreover, repeatability of perfusion parameters was better using FAIR. Discussion This study showed that compared to (balanced) pCASL, FAIR perfusion values were significantly higher and more comparable between visits. Show less
Hutter, J.; Harteveld, A.A.; Jackson, L.H.; Franklin, S.; Bos, C.; Osch, M.J.P. van; ... ; Vita, E. de 2019
