Development of MRI techniques for the assessment of chronic kidney disease

It is well established that patients with Chronic Kidney Disease (CKD) are more susceptible to develop cardiovascular disease in comparison to the healthy population. This thesis aims to develop and apply MRI techniques to assess the human heart and kidney in patients with chronic kidney disease (CKD). Magnetic resonance imaging (MRI) can be used to inform on structure, function, perfusion and blood flow, without the need for ionizing radiation. In order to assess blood flow using MRI, gadolinium based contrast agents are often used. Patients with compromised kidney function are contraindicated to these contrast agents and so it is necessary to develop imaging techniques that can be used without a contrast agent. Arterial spin labelling (ASL) is an MRI technique that provides a non-contrast enhanced method to assess tissue perfusion using the intrinsic signal from the water in the body. ASL is now becoming a well-established technique in the brain, however applications of ASL in the body are currently limited. In this work, a cardiac ASL technique is developed using a modified Look-Locker scheme to study the myocardium of the heart. This technique is then applied in patients with CKD Stage 3 and age-matched healthy control subjects to assess the changes in myocardial perfusion during a handgrip exercise challenge. MRI measurements of cardiac index and stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow and myocardial perfusion using ASL are applied to assess changes in cardiac function in CKD Stage 5 patients during dialysis treatment. The measures are performed in a randomised design to assess the cardiovascular effects in patients undergoing both haemodialysis and haemodiafiltration. Finally, a comparison of 2D readout schemes for renal ASL is performed. Gradient and spin echo based readout schemes for multi-slice ASL of the kidney at 3 T are evaluated and directly compared in terms of temporal SNR, image SNR, spatial coverage, perfusion quantification and variability across slices/subjects. This work aims to determine the optimal readout scheme for pulsed ASL (PASL) of the kidneys at 3 T in healthy volunteers with normal renal function. In future work this could be applied to patients with compromised renal function where a robust imaging technique is needed. Finally, a summary of the key findings of this thesis and an outline of the potential future directions of this work is provided

Development of MRI techniques for the assessment of chronic kidney disease

It is well established that patients with Chronic Kidney Disease (CKD) are more susceptible to develop cardiovascular disease in comparison to the healthy population. This thesis aims to develop and apply MRI techniques to assess the human heart and kidney in patients with chronic kidney disease (CKD). Magnetic resonance imaging (MRI) can be used to inform on structure, function, perfusion and blood flow, without the need for ionizing radiation. In order to assess blood flow using MRI, gadolinium based contrast agents are often used. Patients with compromised kidney function are contraindicated to these contrast agents and so it is necessary to develop imaging techniques that can be used without a contrast agent. Arterial spin labelling (ASL) is an MRI technique that provides a non-contrast enhanced method to assess tissue perfusion using the intrinsic signal from the water in the body. ASL is now becoming a well-established technique in the brain, however applications of ASL in the body are currently limited. In this work, a cardiac ASL technique is developed using a modified Look-Locker scheme to study the myocardium of the heart. This technique is then applied in patients with CKD Stage 3 and age-matched healthy control subjects to assess the changes in myocardial perfusion during a handgrip exercise challenge. MRI measurements of cardiac index and stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow and myocardial perfusion using ASL are applied to assess changes in cardiac function in CKD Stage 5 patients during dialysis treatment. The measures are performed in a randomised design to assess the cardiovascular effects in patients undergoing both haemodialysis and haemodiafiltration. Finally, a comparison of 2D readout schemes for renal ASL is performed. Gradient and spin echo based readout schemes for multi-slice ASL of the kidney at 3 T are evaluated and directly compared in terms of temporal SNR, image SNR, spatial coverage, perfusion quantification and variability across slices/subjects. This work aims to determine the optimal readout scheme for pulsed ASL (PASL) of the kidneys at 3 T in healthy volunteers with normal renal function. In future work this could be applied to patients with compromised renal function where a robust imaging technique is needed. Finally, a summary of the key findings of this thesis and an outline of the potential future directions of this work is provided

The vitality, adulteration and impurities of Clover, Alfalfa and Timothy seed for sale in Iowa in 1906.

Clover and timothy are the most important hay crops grown in Iowa. The census of 1905 gives the area devoted to the growing of red clover in the state as 237,309 acres; of timothy as 3,642,424 acres. These figures do not Include the area devoted to minor clover crops such as alsike and white clover. It may be said, however, that only a small area in the state is devoted to the growing of the former. The white clover crop covers a much larger area than any other of the leguminous plants. It is, however, seldom sown as a forage crop, but it is largely spontaneous in pastures. Borne seasons it is abundant and in others it Constitutes only a small part of the forage in pastures. In addition to its use for this purpose it is sown in lawns as a nurse crop. Alfalfa is cultivated only to a limited extent in Iowa; the area thus devoted is not ascertainable, but is small. The demand for alfalfa seed is continually increasing, largely because of the success attending its cultivation in suitable soils and locations. This success has induced a large number of farmers to try it in an experimental way

Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human Kidney Cortex

Purpose A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these 2D imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T.MethodsTen healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability.Results:For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 ml/100g/min, GE-EPI: 222 ± 18 ml/100g/min, SE-EPI: 201 ± 36 ml/100g/min, TSE: 200 ± 20 ml/100g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment.ConclusionFor the assessment of kidney cortex perfusion using 2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate

Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging

BACKGROUND:Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD).METHODS:We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated.RESULTS:MRI evidenced excellent reproducibility in CKD (coefficient of variation

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics

Background & aimsBlood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output.MethodsHealthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging.ResultsTen of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index.ConclusionsA smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid

Arterial spin labelling MRI to measure renal perfusion: a systematic review and statement paper

Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5–10min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address

Anthropogenic risk increases night-time activities and associations in African elephants (Loxodonta africana) in the Ruaha-Rungwa ecosystem, Tanzania

Elephants face diverse threats from human activities and use temporal and social strategies to reduce human-induced mortality risk. We used data from camera trap surveys in 2018–2019 (n= 1625 independent detection events from 11,751 sampling days) to investigate elephant responses to anthropogenic risk in the Ruaha-Rungwa ecosystem, Tanzania. The study was conducted in one low- risk and three high- risk sites using 26–40 paired camera trap stations per site. Risk influenced the active pe-riods, use of roads and water sources, social associations and behaviour of elephants. Elephants demonstrated significantly more night-time and reduced daytime activ-ity in the high- risk sites relative to the low- risk site. This higher night-time activity in the high- risk sites was observed for both males and females, though it was more pronounced for cow–calf groups than lone males. Foraging events and use of water sources were more frequent at night in the high- risk sites. Elephants used roads as movement routes in the low- risk site but avoided roads in the high- risk sites. Males were significantly more likely to associate with other males and cow–calf groups in the high- risk sites. Fewer occurrences of relaxed behaviours were observed in the high- risk sites compared to the low- risk site. We discuss the potential implications of our findings for elephant survival and reproduction.Output Status: Forthcoming/Available Onlin

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA

Purpose The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. Methods A task force was formed in July 2018 focused on fve methods. A draft process for attaining consensus was distributed publicly for consultation and fnalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refned the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). Results A seven-stage process was defned: (1) formation of expert panels; (2) defnition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specifc terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. Conclusion The process generated meaningful technical recommendations across very diferent MRI methods, while allowing for improvement and refnement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation