Indian agriculture is widely believed to be in crisis. There is broad consensus among scholar, policymakers and activists that economic hardships and the changing climate have made sustaining a... Show moreIndian agriculture is widely believed to be in crisis. There is broad consensus among scholar, policymakers and activists that economic hardships and the changing climate have made sustaining a livelihood through farming increasingly untenable. There is a strong sense that something has to be done to help farmers deal with the crisis, and in recent years agricultural insurance has been presented as a possible fix for rural distress. This dissertation studies how a new agricultural insurance scheme called PMFBY becomes part of everyday social interactions and experiences. Insurance companies often assert that quantified procedures can accurately - and fairly - calculate the extent of agricultural risk, attach a price tag to it and protect against it. Can quantification really be the antidote to crisis? To answer this question I explore how insurance numbers translate to the everyday experiences of rural people in central Maharashtra. I find that, when seen from the perspective of those encountering them in their daily lives, the numbers are anything but straightforward. The effects of quantification were often arbitrary, and despite promises of transparency, they had a tendency to obscure rather than clarify. In short, the numbers turned out to be inconsistent and ambiguous. The dissertation describes how people attempt to make sense of this ambiguity through their moral understandings. It focusses on the (often heated) discussions, the collective pondering such discussions led to, the personal dilemmas it posed as well as the dreams and aspirations numbers became entwined with. I explore how such quandaries unfold and argue that a focus on the morality of quantification brings to light the social life of numbers beyond their 'objective' factuality. Show less
BackgroundIndocyanine green near-infrared fluorescence bowel perfusion assessment has shown its potential benefit in preventing anastomotic leakage. However, the surgeon's subjective visual... Show moreBackgroundIndocyanine green near-infrared fluorescence bowel perfusion assessment has shown its potential benefit in preventing anastomotic leakage. However, the surgeon's subjective visual interpretation of the fluorescence signal limits the validity and reproducibility of the technique. Therefore, this study aimed to identify objective quantified bowel perfusion patterns in patients undergoing colorectal surgery using a standardized imaging protocol.MethodA standardized fluorescence video was recorded. Postoperatively, the fluorescence videos were quantified by drawing contiguous region of interests (ROIs) on the bowel. For each ROI, a time-intensity curve was plotted from which perfusion parameters (n = 10) were derived and analyzed. Furthermore, the inter-observer agreement of the surgeon's subjective interpretation of the fluorescence signal was assessed.ResultsTwenty patients who underwent colorectal surgery were included in the study. Based on the quantified time-intensity curves, three different perfusion patterns were identified. Similar for both the ileum and colon, perfusion pattern 1 had a steep inflow that reached its peak fluorescence intensity rapidly, followed by a steep outflow. Perfusion pattern 2 had a relatively flat outflow slope immediately followed by its plateau phase. Perfusion pattern 3 only reached its peak fluorescence intensity after 3 min with a slow inflow gradient preceding it. The inter-observer agreement was poor-moderate (Intraclass Correlation Coefficient (ICC): 0.378, 95% CI 0.210-0.579).ConclusionThis study showed that quantification of bowel perfusion is a feasible method to differentiate between different perfusion patterns. In addition, the poor-moderate inter-observer agreement of the subjective interpretation of the fluorescence signal between surgeons emphasizes the need for objective quantification. Show less
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease affecting the small arteries in the brain with hallmark depositions of amyloid-β in the vessel wall, leading to cognitive decline and... Show moreCerebral amyloid angiopathy (CAA) is a cerebrovascular disease affecting the small arteries in the brain with hallmark depositions of amyloid-β in the vessel wall, leading to cognitive decline and intracerebral hemorrhage (ICH). An emerging MRI marker for CAA is cortical superficial siderosis (cSS) as it is strongly related to the risk of (recurrent) ICH. Current assessment of cSS is mainly done on T2*- weighted MRI using a qualitative score consisting of 5 categories of severity which is hampered by ceiling effects. Therefore, the need for a more quantitative measurement is warranted to better map disease progression for prognosis and future therapeutic trials. We propose a semi-automated method to quantify cSS burden on MRI and investigated it in 20 patients with CAA and cSS. The method showed excellent inter-observer (Pearson’s 0.991, P < 0.001) and intra-observer reproducibility (ICC 0.995, P < 0.001). Furthermore, in the highest category of the multifocality scale a large spread in the quantitative score is observed, demonstrating the ceiling effect in the traditional score. We observed a quantitative increase in cSS volume in two of the 5 patients who had a 1 year follow up, while the traditional qualitative method failed to identify an increase because these patients were already in the highest category. The proposed method could therefore potentially be a better way of tracking progression.In conclusion, semi-automated segmenting and quantifying cSS is feasible and repeatable and may be used for further studies in CAA cohorts. Show less
Tange, F.P.; Verduijn, P.S.; Mulder, B.G.S.; Capelle, L. van; Koning, S.; Driessen, C.; ... ; Vorst, J.R. van der 2023
Background: A common complication after a DIEP flap reconstruction is the occurrence of fat necrosis due to inadequate flap perfusion zones. Intraoperative identification of ischemic zones in the... Show moreBackground: A common complication after a DIEP flap reconstruction is the occurrence of fat necrosis due to inadequate flap perfusion zones. Intraoperative identification of ischemic zones in the DIEP flap could be opti-mized using indocyanine green near-infrared fluorescence angiography (ICG-NIR-FA). This randomized controlled trial aims to determine whether intraoperative ICG-NIR-FA for the assessment of DIEP flap perfusion decreases the occurrence of fat necrosis. Design/methods: This article describes the protocol of a Dutch multicenter randomized controlled clinical trial: the FAFI-trial. Females who are electively scheduled for autologous breast reconstruction using DIEP or muscle -sparing transverse rectus abdominis muscle (msTRAM) flaps are included. A total of 280 patients will be included in a 1:1 ratio between both study arms. In the intervention arm, the intraoperative assessment of flap perfusion will be based on both regular clinical parameters and ICG-NIR-FA. The control arm consists of flap perfusion evaluation only through the regular clinical parameters, while ICG-NIR-FA images are obtained during surgery for which the surgeon is blinded. The main study endpoint is the difference in percentage of clinically relevant fat necrosis between both study arms, evaluated two weeks and three months after reconstruction. Conclusion: The FAFI-trial, a Dutch multicenter randomized controlled clinical trial, aims to investigate the clinical added value of intraoperative use of standardized ICG-NIR-FA for assessment of DIEP/msTRAM flap perfusion in the reduction of fat necrosis. Clinical trial registration number: NCT05507710; NL 68623.058.18. 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
Purpose: Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging... Show morePurpose: Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases. Methods: These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine. Conclusion: The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality. Show less
Purpose Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging... Show morePurpose Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases. Methods These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine. Conclusion The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality. 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
Zoutman, W.H.; Nell, R.J.; Versluis, M.; Pico, I.; Vu, T.H.K.; Verdijk, R.M.; ... ; Velden, P.A. van der 2022
B cells fulfill an important role in the adaptive immunity. Upon activation and immunoglobulin (IG) class switching, these cells function in the humoral immunity compartment as plasma cells. For... Show moreB cells fulfill an important role in the adaptive immunity. Upon activation and immunoglobulin (IG) class switching, these cells function in the humoral immunity compartment as plasma cells. For clinical applications, it can be important to quantify (switched) B cells accurately in a variety of body fluids and tissues of benign, inflammatory and malignant origin. For decades, flow cytometry and immunohistochemistry (IHC) have been the preferred methods for quantification. Although these methods are widely used, both depend on the accessibility of B cell epitopes and therefore require intact (fixed) cells. Whenever samples are low in quantity and/or quality, accurate quantification can be difficult. By shifting the focus from epitopes to DNA markers, quantification of B cells remains achievable. During differentiation and maturation, B cells are subjected to programmed genetic recombination processes like VDJ rearrangements and class switch recombination (CSR), which result in deletion of specific sequences of the IGH locus. These cell type-specific DNA "scars" (loss of sequences) in IG genes can be exploited as B cell markers in digital PCR (dPCR) based quantification methods. Here, we describe a novel, specific and sensitive digital PCR-based method to quantify mature and switched B cells in DNA specimens of benign and (copy number unstable) malignant origin. We compared this novel way of B cell quantitation with flow cytometric and immunohistochemical methods. Through cross-validation with flow cytometric sorted B cell subpopulations, we gained quantitative insights into allelic involvement in different recombination processes in the IGH locus. Our newly developed method is accurate and independent of the cellular context, offering new possibilities for quantification, even for (limited) small samples like liquid biopsies. Show less
Polling, M.; Sin, M.; Weger, L.A. de; Speksnijder, A.G.C.L.; Koenders, M.J.F.; Boer, H. de; Gravendeel, B. 2022
Airborne pollen monitoring is of global socio-economic importance as it provides information on presence and prevalence of allergenic pollen in ambient air. Traditionally, this task has been... Show moreAirborne pollen monitoring is of global socio-economic importance as it provides information on presence and prevalence of allergenic pollen in ambient air. Traditionally, this task has been performed by microscopic investigation, but novel techniques are being developed to automate this process. Among these, DNA metabarcoding has the highest potential of increasing the taxonomic resolution, but uncertainty exists about whether the results can be used to quantify pollen abundance. In this study, it is shown that DNA metabarcoding using trnL and nrITS2 provides highly improved taxonomic resolution for pollen from aerobiological samples from the Netherlands. A total of 168 species from 143 genera and 56 plant families were detected, while using a microscope only 23 genera and 22 plant families were identified. NrITS2 produced almost double the number of OTUs and a much higher percentage of identifications to species level (80.1%) than trnL (27.6%). Furthermore, regressing relative read abundances against the relative abundances of microscopically obtained pollen concentrations showed a better correlation for nrITS2 (R-2= 0.821) than for trnL (R-2 = 0.620). Using three target taxa commonly encountered in early spring and fall in the Netherlands (Alnus sp., Cupressaceae/Taxaceae and Urticaceae) the nrITS2 results showed that all three taxa were dominated by one or two species (Alnus glutinosa/incana, Taxus baccata and Urtica dioica). Highly allergenic as well as artificial hybrid species were found using nrITS2 that could not be identified using trnL or microscopic investigation (Alnus x spaethii, Cupressus arizonica, Parietaria spp.). Furthermore, perMANOVA analysis indicated spatiotemporal patterns in airborne pollen trends that could be more clearly distinguished for all taxa using nrITS2 rather than trnL. All results indicate that nrITS2 should be the preferred marker of choice for molecular airborne pollen monitoring. (C) 2021 The Authors. Published by Elsevier B.V. Show less
Hita, A.; Brocart, G.; Fernandez, A.; Rehmsmeier, M.; Alemany, A.; Schvartzman, S. 2022
Background: Total-RNA sequencing (total-RNA-seq) allows the simultaneous study of both the coding and the non-coding transcriptome. Yet, computational pipelines have traditionally focused on... Show moreBackground: Total-RNA sequencing (total-RNA-seq) allows the simultaneous study of both the coding and the non-coding transcriptome. Yet, computational pipelines have traditionally focused on particular biotypes, making assumptions that are not full-filled by total-RNA-seq datasets. Transcripts from distinct RNA biotypes vary in length, biogenesis, and function, can overlap in a genomic region, and may be present in the genome with a high copy number. Consequently, reads from total-RNA-seq libraries may cause ambiguous genomic alignments, demanding for flexible quantification approaches. Results: Here we present Multi-Graph count (MGcount), a total-RNA-seq quantification tool combining two strategies for handling ambiguous alignments. First, MGcount assigns reads hierarchically to small-RNA and long-RNA features to account for length disparity when transcripts overlap in the same genomic position. Next, MGcount aggregates RNA products with similar sequences where reads systematically multimap using a graph-based approach. MGcount outputs a transcriptomic count matrix compatible with RNA-sequencing downstream analysis pipelines, with both bulk and single-cell resolution, and the graphs that model repeated transcript structures for different biotypes. The software can be used as a python module or as a single-file executable program. Conclusions: MGcount is a flexible total-RNA-seq quantification tool that successfully integrates reads that align to multiple genomic locations or that overlap with multiple gene features. Its approach is suitable for the simultaneous estimation of protein-coding, long non-coding and small non-coding transcript concentration, in both precursor and processed forms. Both source code and compiled software are available at https://github.com/hitaandrea/MGcount. Show less
The challenge of achieving fast quantification in metabolomics is the presence of severe matrix effects during the MS analysis of complex samples. Complex samples also result in challenges during... Show moreThe challenge of achieving fast quantification in metabolomics is the presence of severe matrix effects during the MS analysis of complex samples. Complex samples also result in challenges during metabolite identification as complex MS/MS spectra and peak overlap in 1H NMR complicate structure elucidation. The goal of this thesis is to tackle these challenges by the development and application of innovative fractionation approaches and state-of-the-art MS and NMR analyses. Show less
Inflammatory arthritis comprises a group of diseases in which the immune system attacks the body’s own tissues. Two prevalent types of inflammatory arthritis are rheumatoid arthritis (RA) and... Show moreInflammatory arthritis comprises a group of diseases in which the immune system attacks the body’s own tissues. Two prevalent types of inflammatory arthritis are rheumatoid arthritis (RA) and spondyloarthritis (SpA). Clinical research points to the importance of early diagnosis, as treatment in early disease stages increases chances of better outcome and improved quality of life for patients. To this end, the diagnostic potential of imaging modalities sensitive to local inflammation, such as magnetic resonance imaging (MRI), is of great interest. The goal of this thesis was to develop computer-aided methods for assessment of MRI-detected inflammation with the aim of aiding early diagnosis of inflammatory arthritis. In particular, we focused on the tasks of comparative visualization, automatic quantification, and feature selection. The presented studies showcase the potential of comparative visualization and automatic quantification to overcome the limitations of visual scoring and lay out a fertile ground for future improvements. Additionally, the understanding of the diagnostic role of individual inflammatory features in prediction of RA development is further advanced. Collectively, these findings can help facilitate the use of MRI for early diagnosis of inflammatory arthritis and potentially increase chances of better outcome and quality of life for patients. Show less
Hoogstins, C.; Burggraaf, J.J.; Koller, M.; Handgraaf, H.; Boogerd, L.; Dam, G. van; ... ; Burggraaf, J. 2019
The aim of this thesis is to develop image processing solutions that enable the fully automatic pre-operative planning of aorta-related procedures, such as Trans-catheter aortic valve... Show moreThe aim of this thesis is to develop image processing solutions that enable the fully automatic pre-operative planning of aorta-related procedures, such as Trans-catheter aortic valve replacement and aorta dilatation diagnosis. Hence, the objectives of this thesis are as follows: 1. To fully automatically quantify the aorto-iliac vascular access route, including the aortic root by image processing methods in CTA. 2. To broaden the scope of automatic methods into the detection of aorta dilatation. 3. To integrate the automatic quantification methods into applications which allow manual interactions and the calculation of clinically relevant parameters. 4. To demonstrate the accuracy and feasibility of the fully automatic planning and quantification methods in different patient cohorts. Show less
Endocannabinoids, a class of lipid messengers, have emerged as crucial regulators of synaptic communication in the central nervous system (CNS). Dysregulation of these compounds has been... Show moreEndocannabinoids, a class of lipid messengers, have emerged as crucial regulators of synaptic communication in the central nervous system (CNS). Dysregulation of these compounds has been implicated in many brain disorders. Although some studies have identified and quantified a limited number of target compounds, a method that provides comprehensive quantitative information on endocannabinoids and related N-acylethanolamines (NAEs) in CSF is currently lacking as measurements are challenging due to low concentrations under normal physiological conditions. Here we developed and validated a high-throughput nano liquid chromatography-electrospray ionization mass spectrometry (nano LC-ESI-MS/MS) platform for the simultaneous quantification of endocannabinoids (anandamide (AEA), 2-arachidonoyl glycerol (2-AG)), ten related NAEs and eight additional putatively annotated NAEs in human CSF. Requiring only 200 μL of CSF our method has limits of detection from 0.28 to 61.2 pM with precisions of RSD <15% for most compounds. We applied our method to CSF from 45 healthy humans and demonstrated potential age and gender effects on concentrations of endocannabinoids and NAEs. Notably, our results show that docosahexaenoyl ethanolamide (DHEA) concentrations increase with age in males. Our method may offer new opportunities to gain insight into regulatory functions of endocannabinoids in the context of (ab)normal brain function. Show less
Mirzaian, M.; Wisse, P.; Guimaraes Da Lomba Ferraz, M.J.; Marques, A.R.A.; Gaspar, P.; Oussoren, S.V.; ... ; Aerts, J.M.F.G. 2017
The objective of this dissertation was to establish the value of QCT to further enhance the clinical applicability and accuracy of coronary CTA. The automatic characterization of coronary... Show more The objective of this dissertation was to establish the value of QCT to further enhance the clinical applicability and accuracy of coronary CTA. The automatic characterization of coronary atherosclerosis with QCT is feasible and correlates well with IVUS VH. Secondly, novel CTA risk score was created incorporating detailed information on the location, severity and composition of atherosclerosis as assessed with QCT. This CTA risk score allows accurate risk stratification of patients with suspected CAD. A drawback of coronary CTA is the fact that the hemodynamic significance of a lesion cannot be evaluated. In this thesis it was demonstrated that QCT provided better correlation with the presence of myocardial ischemia on SPECT MPI as compared to current visual assessment of coronary CTA. With regards to the specific setting of high risk diabetic patients without chest pain syndrome several conclusion can be derived from this thesis. First, if treated with optimal medical therapy, very few patients present with progression of myocardial ischemia. Second, the prognosis of these patients is good; the overall long-term event-rate is limited. Especially diabetic patients without CAD on coronary CTA have an excellent prognosis. Show less
