AimsWe sought to evaluate the mechanism of angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart... Show moreAimsWe sought to evaluate the mechanism of angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF).Methods and resultsThe study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II–III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (−4.5 mmHg; p = 0.026) and systolic blood pressure (−9.8 mmHg; p = 0.0007), myocardial perfusion (−0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (−296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (−5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088).ConclusionsWe found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients. Show less
In this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo... Show moreIn this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo-continuous (ASL) preparation was combined with multiple different readout modules, such as Look-Locker, Simultaneous multi-slice acquisition or a golden angle based non-Cartesian k-space trajectory to obtain high temporal resolution multi-time point data. These datasets were then used to improve the quantification of ASL signal and to obtain cerebral blood flow, arterial transit time and arterial blood volume maps. These quantitative maps hold the potential to provide important information in for example patients with stroke or Alzheimer’s disease. In addition, one of the assumptions within the two-component kinetic model to obtain these quantitative maps was investigated to study the separation of the macrovascular and perfusion component of the ASL signal. Show less
Hoven, P. van den; Osterkamp, J.; Nerup, N.; Svendsen, M.B.S.; Vahrmeijer, A.; Vorst, J.R. van der; Achiam, M.P. 2023
PurposeIncorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a... Show morePurposeIncorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a possible solution. However, only through quantification of the fluorescence signal can an objective and reproducible evaluation of tissue perfusion be obtained. This narrative review aims to provide an overview of the available quantification methods for perfusion assessment using ICG NIR fluorescence imaging and to present an overview of current clinically utilized software implementations.MethodsPubMed was searched for clinical studies on the quantification of ICG NIR fluorescence imaging to assess tissue perfusion. Data on the utilized camera systems and performed methods of quantification were collected.ResultsEleven software programs for quantifying tissue perfusion using ICG NIR fluorescence imaging were identified. Five of the 11 programs have been described in three or more clinical studies, including Flow (R) 800, ROIs Software, IC Calc, SPY-Q (TM), and the Quest Research Framework (R). In addition, applying normalization to fluorescence intensity analysis was described for two software programs.ConclusionSeveral systems or software solutions provide a quantification of ICG fluorescence; however, intraoperative applications are scarce and quantification methods vary abundantly. In the widespread search for reliable quantification of perfusion with ICG NIR fluorescence imaging, standardization of quantification methods and data acquisition is essential. Show less
Chronic kidney disease has restricted treatment options and leads to a lower quality of life, even before the end stage of renal disease is reached. The ability to generate new transplantable... Show moreChronic kidney disease has restricted treatment options and leads to a lower quality of life, even before the end stage of renal disease is reached. The ability to generate new transplantable kidney tissue could help millions of people worldwide and is therefore of great interest. This thesis explores options within regenerative medicine to develop new transplantable kidney tissue from a bio-engineering point of view. Show less
Hoven, P. van den; Verduijn, P.S.; Capelle, L. van; Tange, F.P.; Michi, M.; Corion, L.U.M.; ... ; Vorst, J.R. van der 2022
Background: One of the complications of free flap breast reconstruction is the oc-currence of skin and fat necrosis. Intra-operative use of near-infrared (NIR) fluorescence imag-ing with... Show moreBackground: One of the complications of free flap breast reconstruction is the oc-currence of skin and fat necrosis. Intra-operative use of near-infrared (NIR) fluorescence imag-ing with Indocyanine Green (ICG) has the potential to predict these complications. In this study, the quantification of the fluorescence intensity measured in free flap breast reconstruction was performed to gain insight into the perfusion patterns observed with ICG NIR fluorescence imag-ing.Methods: ICG NIR fluorescence imaging was performed in patients undergoing free flap breast reconstruction following mastectomy. After completion of the arterial and venous anastomosis, 7.5 mg ICG was administered intravenously. The fluorescence intensity over time was recorded using the Quest Spectrum Platform (R). Four regions of interest (ROI) were selected based on location and interpretation of the NIR fluorescence signal: (1) The perforator, (2) normal per -fusion, (3) questionable perfusion, and (4) low perfusion. Time-intensity curves were analyzed, and two parameters were extracted: Tmax and Tmax slopes.Results: Successful ICG NIR fluorescence imaging was performed in 13 patients undergoing 17 free flap procedures. Region selection included 16 perforators, 17 normal perfusions, 8 ques-tionable perfusions, and 5 low perfusion ROIs. Time-intensity curves of the perforator ROIs were comparable to the ROIs of normal perfusion and demonstrated a fast inflow. No outflow was observed for the ROIs with questionable and low perfusion.Conclusion: This study provides insight into the perfusion patterns observed with ICG NIR flu-orescence imaging in free flap breast reconstruction. Future studies should correlate quantita-tive parameters with clinical perfusion assessment and outcome.(c) 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable... Show moreNear-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable quantitative assessment of tissue perfusion using this technique, predominantly in patients with lower extremity arterial disease. Two systematic reviews were performed, describing the experience with ICG NIR fluorescence imaging within various surgical fields. In three original studies, perfusion patterns were described in various groups, including lower extremity arterial disease, healthy controls and in patients undergoing free flap reconstructive breast surgery. By applying normalization to the quantitative assessment, an increased validity and reliability was seen. To describe potential clinical applications, the use of ICG NIR fluorescence imaging was described for two indications. In patients undergoing unilateral revascularization, quantitative assessment showed an increase of inflow parameters, whilst parameters in the untreated side remained unchanged. In a cohort of patients undergoing amputation surgery, ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Future use of ICG NIR fluorescence imaging should focus on improving validity and reliability of quantitative perfusion assessment. Show less
Chappell, M.A.; McConnell, F.A.K.; Golay, X.; Gunther, M.; Hernandez-Tamames, J.A.; Osch, M.J. van; Asllani, I. 2021
The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE),... Show moreThe mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, 'uncorrected', images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods. Show less
Muehlberg, F.; Stoetzner, A.; Forman, C.; Schmidt, M.; Riazy, L.; Dieringer, M.; ... ; Schulz-Menger, J. 2020
Purpose: Stress perfusion imaging plays a major role in non-invasive detection of coronary artery disease.We compared a compressed sensing-based and a conventional gradient echo perfusion sequence... Show morePurpose: Stress perfusion imaging plays a major role in non-invasive detection of coronary artery disease.We compared a compressed sensing-based and a conventional gradient echo perfusion sequence with regard to image quality and diagnostic performance.Method: Patients sent for coronary angiography due to pathologic stress perfusion CMR were recruited. All patients underwent two adenosine stress CMR using conventional TurboFLASH and prototype SPARSE sequence as well as quantitative coronary angiography with fractional flow reserve (FFR) within 6 weeks. Coronary angiography was considered gold standard with FFR < 0.75 or visual stenosis >90 % for identification of myocardial ischemia. Diagnostic performance of perfusion imaging was assessed in basal, mid-ventricular and apical slices by quantification of myocardial perfusion reserve (MPR) analysis utilizing the signal upslope method and a deconvolution technique using the fermi function model.Results: 23 patients with mean age of 69.6 +/- 8.9 years were enrolled. 46 % were female.Image quality was similar in conventional TurboFLASH sequence and SPARSE sequence (2.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0,06). SPARSE sequence showed higher contrast-to-noise ratio (52.1 +/- 27.4 vs 40.5 +/- 17.6, p < 0.01) and signal-to-noise ratio (15.6 +/- 6.2 vs 13.2 +/- 4.2, p < 0.01) than TurboFLASH sequence. Dark-rim artifacts occurred less often with SPARSE (9 % of segments) than with TurboFLASH (23 %).In visual assessment of perfusion defects, SPARSE sequence detected less false-positive perfusion defects (n = 1) than TurboFLASH sequence (n = 3).Quantitative perfusion analysis on segment basis showed equal detection of perfusion defects for TurboFLASH and SPARSE with both upslope MPR analysis (TurboFLASH 0.88 +/- 0.18; SPARSE 0.77 +/- 0.26; p = 0.06) and fermi function model (TurboFLASH 0.85 +/- 0.24; SPARSE 0.76 +/- 0.30; p = 0.13).Conclusions: Compressed sensing perfusion imaging using SPARSE sequence allows reliable detection of myocardial ischemia. Show less
Hoven, P. van den; Ooms, S.; Manen, L. van; Bogt, K.E.A. van der; Schaik, J. van; Hamming, J.F.; ... ; Mieog, J.S.D. 2019
Objective: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe... Show moreObjective: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe media sclerosis. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) can provide information about tissue perfusion and has already been studied in oncologic, reconstructive, and cardiac surgery. For patients with PAD, this technique might give insight into skin perfusion and thereby guide treatment. We performed a systematic review of the literature on the use of NIR fluorescence imaging in patients with PAD.Methods: PubMed, MEDLINE, Embase, and Cochrane were searched for articles and abstracts on the application of NIR fluorescence imaging using ICG as fluorescent dye in patients with PAD. Our search strategy combined the terms "fluorescence," "ICG," or synonyms and "peripheral artery disease" or synonyms. The extracted data included fluorescence parameters and test characteristics for diagnosis of PAD.Results: Twenty-three articles were found eligible for this review using 18 different parameters for evaluation of the fluorescence signal intensity. NIR fluorescence imaging was used for four main indications: diagnosis, quality control in revascularization, guidance in amputation surgery, and visualization of vascular structures. For the diagnosis of PAD, NIR fluorescence imaging yields a sensitivity ranging from 67% to 100% and a specificity varying between 72% and 100%. Significant increases in multiple fluorescence parameters were found in comparing patients before and after revascularization.Conclusions: NIR fluorescence imaging can be used for several indications in patients with PAD. NIR fluorescence imaging seems promising in diagnosis of PAD and guidance of surgeons in treatment, especially in patients in whom current diagnostic methods are not applicable. Further standardization is needed to reliably use this modality in patients with PAD. Show less
In this thesis I have described the introduction and validation of a new spatially non-selective arterial spin labeling (SNS-ASL) method in healthy subjects. Acceleration selective ASL (AccASL... Show moreIn this thesis I have described the introduction and validation of a new spatially non-selective arterial spin labeling (SNS-ASL) method in healthy subjects. Acceleration selective ASL (AccASL) was compared with pseudo continuous ASL (pCASL), a traditional ASL method, as well as other spatially non-selective ASL methods (velocity selective ASL, as introduced by Wong et al with two velocity-selective blocks, and using only a single labeling module), and with [15O]-H2O PET as the gold standard for brain perfusion imaging. By combining an AccASL with VSASL labeling module, the location of label origin in the vascular tree was assessed. Furthermore, time-encoded pCASL was explored in combination with SNS-ASL labeling modules to obtain insight into labeling at multiple post labeling delays (PLD). Finally, te-pCASL was combined with T2-Relaxation-under-Spin-Tagging (TRUST) to provide a time efficient method to distinguish spin compartments based on their T2-values. Show less
