Synopsis
Unlike most organs, in the kidneys, oxygen consumption changes with
blood flow and increased blood flow doesn't necessary lead to increased oxygen
delivery. This leads to a need for independent measures of perfusion and
oxygentation BOLD
MRI is the only non-invasive method to evaluate renal oxygenation. It is most useful for
detecting acute changes following pharmacologic/physiologic maneuvers. Based on evidence from pre-clinical models,
translation to the clinic is being pursued.
Limitations in conventional ROI analysis have been identified, creating
an interest in alternative methods, including whole kidney analysis. Alternate methods to measure oxygenation
include electron paramagnetic resonance and fluorine-19 MRI, both involving
exogenous materials to be used.Highlights
1. Kidneys are unique in that the regional tissue oxygenation is not
flow limited and hence there is an inherent need to independently evaluate renal
oxygenation.
2. BOLD MRI is the only known non-invasive method that allows
for evaluation of intra-renal oxygenation in humans. Most useful for detecting acute changes
following pharmacologic/physiologic maneuvers.
3. T2* or R2* can be used as a quantitative parameter but their
direct relationship to oxygenation is not simple. A recent study has attempted to validate that
relationship.
4. Clinical applications to date include reno-vascular hypertension,
renal transplants, ureteral obstruction, and diabetic nephropathy/chronic
kidney disease. Pre-clinical data
applied to iodinated contrast induced acute kidney injury are promising.
5. Alternate methods to measure oxygenation include electron
paramagnetic resonance and fluorine-19 MRI, both involving exogenous materials
to be used.
TARGET AUDIENCE:
Radiologists, nephrologists, physicists, MR scientists, and MR
technologists who are interested in clinical and/or research studies of the
kidney.
OUTCOME/OBJECTIVES:
Attendees will gain an appreciation for the significance of renal
oxygenation independent of renal blood
flow. They will learn how to evaluate
relative oxygenation status of the kidney using MRI and see examples of both
pre-clinical and clinical applications being pursued. Advantages, perspectives and limitations of MRI
methods in the evaluation of intra-renal oxygenation will also be discussed.
PURPOSE:
In most organs oxygenation is tightly linked to blood flow, in which
case perfusion imaging may be sufficient to understanding regional oxygenation.
In the kidneys, especially in the
medulla, oxygen consumption could change along with or independent of flow
(Figure 1). So there is a need to
evaluate renal oxygenation apart from perfusion. Kidneys have the lowest difference in pO2
difference between the renal artery and vein [1], suggesting that they may
be well oxygenated. However, kidneys actually
have regions that can be characterized to be hypoxic [2]. Only when spatially resolved measurements are
used do the gradients in tissue oxygenation become apparent. Early measurements were made using
microelectrodes inserted into rat kidneys [3]. With the availability of non-invasive imaging,
translation of these invasive studies to humans became possible [4]. Blood oxygenation level dependent (BOLD) MRI
has been the most widely used technique to evaluate renal oxygenation to-date.
METHODS:
BOLD MRI is inherently sensitive to the oxygenation status of blood. If one assumes that blood oxygenation is in a
dynamic equilibrium with the surrounding tissue oxygenation, BOLD MRI can be
used to evaluate changes in tissue oxygenation.
Early studies with BOLD MRI in humans [4] duplicated results using
microelectrodes in rat kidneys. While
the early studies used EPI based acquisitions, R2* mapping through mGRE is now common,
resulting in higher quality images and a quantitative analysis.[5]. Combined with breath-holding, a single slice
acquisition can be performed in about 10 to 15 s (Figure 2).
APPLICATIONS:
mGRE sequence is now a standard on all major vendor platforms and all of
them offer inline mapping options, making BOLD MRI readily
available for renal oxygenation studies. This in turn has afforded an opportunity to
duplicate the initial findings independently by several investigators
throughout the world.
To-date, BOLD MRI has
been applied in the clinic to evaluate renal vascular hypertension [6], renal transplants [7, 8], ureteral obstruction [9] and diabetic nephropathy/chronic kidney disease [10, 11]. Renal
medullary hypoxia has an inherent relevance to acute kidney injury and pre-clinical
data lend a strong support [12, 13]. However, clinical
translation is lacking primarily due to logistical issues rather than technical
feasibility.
DISCUSSION & CONCLUSION:
Renal BOLD MRI is feasible and independently verified in healthy human
subjects and in pre-clinical models.
However, applications to the clinic are not without certain practical
limitations. We may need consensus on
the preparation of subjects prior to the study and in analytical methods. Traditional regions of interest (ROI)
analysis is inherently subjective and whole kidney methods offer one
alternative (e.g. Figure 3) [14-16]. In
pre-clinical setting, pre-defined ROIs have been proposed (Figure 4) [17]. While R2*/T2* can be used as a quantitative
marker, translation to absolute pO2 has remained elusive. A recent
study has shown the feasibility that R2’ (= R2*-R2) can be calibrated to blood
pO2 and, with further modeling, can be potentially related to tissue pO2 [18].
Feasibility has been demonstrated with electron paramagnetic resonance
(EPR) [19] and Fluorine-19 MRI [20] to measure renal pO2. However, EPR requires implantation of Lithium phthalocyanine (LiPc) crystals
and F-19 MRI requires administration of exogenous substance.
Acknowledgements
No acknowledgement found.References
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