Phase-based vascular input function: Improved quantitative DCE-MRI of atherosclerotic plaques.

PURPOSE: Quantitative pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI can be used to assess atherosclerotic plaque microvasculature, which is an important marker of plaque vulnerability. Purpose of the present study was (1) to compare magnitude- versus phase-based vascular input functions (m-VIF vs ph-VIF) used in pharmacokinetic modeling and (2) to perform model calculations and flow phantom experiments to gain more insight into the differences between m-VIF and ph-VIF. METHODS: Population averaged m-VIF and ph-VIFs were acquired from 11 patients with carotid plaques and used for pharmacokinetic analysis in another 17 patients. Simulations, using the Bloch equations and the MRI scan geometry, and flow phantom experiments were performed to determine the effect of local blood velocity on the magnitude and phase signal enhancement. RESULTS: Simulations and flow phantom experiments revealed that flow within the lumen can lead to severe underestimation of m-VIF, while this is not the case for the ph-VIF. In line, the peak concentration of the m-VIF is significantly lower than ph-VIF (p < 0.001), in vivo. Quantitative model parameters for m- and ph-VIF differed in absolute values but were moderate to strongly correlated with each other [K(trans) Spearman's ρ > 0.93 (p < 0.001) and vp Spearman's ρ > 0.58 (p < 0.05)]. CONCLUSIONS: m-VIF is strongly influenced by local blood velocity, which leads to underestimation of the contrast medium concentration. Therefore, it is advised to use ph-VIF for DCE-MRI analysis of carotid plaques for accurate quantification.

The potential pool of non-heart-beating kidney donors.

One of the ways to fight the growing organ shortage in transplantation is by procuring organs from non-heart-beating (NHB) donors. In order to determine the NHB kidney donor pool and evaluate its significance for renal transplantation, the potential is estimated in this study by retrospective death chart review. All 200 in-hospital deaths aged 3-65 yr reported at the University Hospital Maastricht in 1994, including 25 deaths at the Emergency Department (ED), were analyzed. After exclusion of deaths by computerized ICD-9-CM codes, 109 charts were abstracted and reviewed by experts. As a result a potential of eight brain dead, heart-beating (HB) donors and 56 NHB donors were identified. Medical suitability and logistic availability were scored in an attempt to quantify the likelihood of the donation to proceed towards successful organ procurement. These scores resulted in a range of potential NHB donors from 4.5 to 9.2 per 100 in-hospital deaths. Including rates of refusal to consent, as well as rates of technical failures, 24.0-49.6 kidneys were calculated to be realistically available annually, 2-4.5 times the projected number of kidneys from HB donors. With this increase of available grafts, at least growth of the renal waiting list would be prevented. This estimate shows that the potential of NHB kidney donors is large, and its impact on organ shortage would be considerable. Since 68% of potential NHB kidney donors, and also 70% of the medically most suitable donors, were found in ED, ICU, and CCU, focusing on these hospital units for implementation of routine procurement of kidneys from NHB donors is probably most effective. We therefore plead for the introduction of NHB kidney procurement protocols in EDs, ICUs, and CCUs.

Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys.

Non-heart-beating (NHB) donors are a valuable source of kidneys for transplantation. The organs, however, sustain substantial warm ischemic damage that may jeopardize the transplantability and result in nonfunction of the grafts. Quantification of warm ischemic time (WIT) and prediction of transplant outcome are essential for the use of NHB donor organs. During machine preservation (MP) the viability of NHB donor kidneys was evaluated through calculating intrarenal vascular resistance and determining lactate dehydrogenase and alpha-glutathione S-transferase (alphaGST) in the perfusate. Thirty-seven functioning (F) and nine nonfunctioning kidneys (NF) were compared. WIT was longer in NF; serum creatinine, donor age, and preservation time were not different. WIT correlated well with alphaGST after 4 and 8 hr of MP (r=0.353, P=0.009, and r=0.346, P=0.011, respectively). When compared with F, intrarenal vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05); at all time points, alphaGST levels were elevated in NF (P<0.05). Lactate dehydrogenase activity was not different between the groups, but could identify immediate functioning grafts within the F group. In conclusion, alphaGST levels correlated strongly with WIT and were also able to distinguish NF from F grafts. alphaGST can adequately predict the functional outcome of NHB donor grafts before transplantation; levels of alphaGST can be used to define reliable safety margins for viability. Therefore, MP is useful in evaluating the viability of NHB donor kidneys, and the parameters discussed will help to select nonviable grafts from this valuable pool of kidneys for transplantation.

The PAF antagonist TCV-309 reduces graft PMN infiltration and enhances early function of 24-hour-preserved rat kidneys with long warm ischemia.

The purpose of this study was to investigate whether treatment with TCV-309, a PAF antagonist, improves life-sustaining function of renal grafts that have suffered warm ischemia (WI) prior to cold storage (CS) and whether TCV-309 influences leukocyte sequestration in tissues. Syngeneic kidneys with 20 min of WI and 24 hr of CS were transplanted into bilateral nephrectomized rats. In the treated group, TCV-309 was administered (i.v. 1 mg/kg) 5 min before reperfusion. Rats in the control group received saline. On day 14, 80% rats survived in the treated group, which was higher than the controls (0%). At 24 hr of reperfusion, myeloperoxidase (MPO) activity, a marker enzyme for PMNs, in the treated kidney was significantly lower than the controls, but did not differ from the normal values. The MPO activity in the controls was higher than the normal values. In conclusion, the PAF antagonist improves posttransplant function of rat kidneys subjected to a period of WI and CS. PMNs are involved in postischemic renal injury, which is, at least partially, mediated by PAF. The effectiveness of PAF antagonist in treatment of recipients may lead to its clinical application in transplantation of ischemically injured kidneys.

Nonheart-beating donors: the Maastricht experience.

The growing gap between the number of organs available for transplantation and patients on waiting lists demands additional donor sources. Nonheart-beating (NHB)-donor programs are known to increase the number of kidneys available. The group of potential NHB donors is very diverse and therefore 4 categories have been identified. At the University Hospital Maastricht, a NHB-donor program was implemented in 1980 to harvest kidneys after an in situ perfusion technique. In order to evaluate the function of kidney grafts from NHB donors, a retrospective multicenter study on the NHB-donor kidneys transplanted until 1992 was performed, using a control group of kidneys from heart-beating (HB) donors. The short-term results showed more delayed function (DF) in the NHB-donor group accompanied by higher serum creatinine levels at one-month posttransplant. The long-term outcome, however, was equal in both groups showing similar graft and patient survival rates up to 5 years. Apart from the type of donor, HB or NHB, only the number of HLA-DR mismatches could be identified as a potential risk factor for delayed graft function. NHB donors contribute considerably to reducing the gap between offer and demand in kidney transplantation and transplant centers should include NHB donors in their procurement programs. Meanwhile, efforts should be made to improve the short-term posttransplant graft function. Together with reducing DF, searching for valuable tools in viability assessment should also be an objective. Past viability tests never found broad clinical use but might be important in the optimal and safe usage of the potential NHB donor pool.