BOLD (blood oxygen level–dependent) in nephrology
-
Upload
venkataramanan-krishnamoorthy -
Category
Documents
-
view
223 -
download
0
Transcript of BOLD (blood oxygen level–dependent) in nephrology
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
1/46
BOLD (blood oxygen leveldependent)
Imaging
Presentor : Venkataramanan
Moderator : Prof. Dr. Sham Sunder
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
2/46
The renal medulla functions in a hypoxic
milieu and is susceptible to changes in blood
flow and blood oxygenation.
Medullary hypoxia has been implicated as a
common pathway in renal failure in animal
models of various renal diseases, including
hypertension and diabetes.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
3/46
BOLD MRI
used for noninvasive but indirect measurement
of renal oxygenation.
exploits the paramagnetic effect of
deoxyhemoglobin for acquisition of images
sensitive to local oxygen concentration.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
4/46
With an increase in tissue deoxyhemoglobin
concentration, result in increased magnetic spin,
there is more dephasing and a decrease in the
T2* relaxation time of the protons in thesurrounding tissues
higher tissue oxygenation results in increased T2*
relaxation time and a correspondingly shortervalue (R2*) Magnetic rate of relaxation .
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
5/46
Magnetic rate of relaxation(R2*) positively
correlates with deoxyhemoglobin levels and
was therefore used as a surrogate measure
of tissue oxygenation.
The increased R2 level implies an increased
deoxyhaemoglobin level and decreased
oxygen bioavailability in the tissue.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
6/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
7/46
Blue represents the lowest R2 level, indicating the lowest tissue
deoxyhaemoglobin concentration, and green and orange distinctivelyrepresent increasing R2 levels, showing the increase of tissue
deoxyhaemoglobin concentration. In a normal functioning allograft, the
cortex is blue with areas of green and the medulla is green and orange
reflecting the decrease in tissue oxygen bioavailability from outermedulla to inner medulla.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
8/46
Furosemide was administered to examine the
effect of inhibiting energy-dependent
electrolyte transport on tissue oxygenation in
subjects.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
9/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
10/46
RENAL ALLOGRAFT DYSFUNCTION
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
11/46
The medullary R2* value in patients who have
undergone transplantation is lower than that
in healthy volunteers, implying relatively
improved oxygenation in transplanted
kidneys.
Reduced tubular fractional reabsorption of
sodium and an increase in blood flow due toallograft denervation.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
12/46
In early renal dysfunction after transplantation,
differentiating acute rejection from ATN is an
important but difficult clinical endeavor
because the initial manifestations of both of
these conditions are abnormal serum
creatinine concentration and a decrease in
GFR
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
13/46
Sadowski et al. found that patients with acuterejection have significantly lower R2* values(higher oxygenation) in the medulla than
patients with ATN and normal allografts. Using an R2* cutoff of 18 seconds1 or lower,
the investigators diagnosed acute rejectionwith 100% sensitivity and specificity.
Sadowski EA, Fain SB, Alford SK, et al. Assessment of acute renaltransplant rejection with blood oxygen leveldependent MR imaging:initial experience. Radiology 2005; 236:911919
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
14/46
This decrease in renal hypoxia in acute
rejection has been attributed to decreased
oxygen utilization or increased
corticomedullary shunting of blood.
In contrast, patients with ATN have higher
cortical R2* value than patients with normal
transplants and patients with acute rejection,likely because of ischemic insult.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
15/46
ATN allograft shows increased green areas in the cortex and more
orange areas in the medulla reflecting the decrease in tissue oxygen
bioavailability both in the cortex and in the medulla
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
16/46
Colour gradient disappears with increased blue areas
in the medulla
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
17/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
18/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
19/46
Eighty-two patients with normal graft function
and 28 patients with biopsy-proven AR (n =
21) or ATN (n = 7) were enrolled.
Patients with AR and ATN underwent BOLD
MRI within 6 days before or after kidney
transplant biopsy.
Cortical R2 (CR2) and medullary R2 (MR2)
levels were measured.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
20/46
The mean CR2 level was significantly higher in the ATN group
(15.25 1.03/s) compared to the normal group (13.35 2.31/s,
P = 0.028) and AR group (12.02 1.72/s, P = 0.001).
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
21/46
The mean MR2 level was significantly lowerin the AR group (14.02
2.68/s) compared to the normal group (16.662.82/s, P
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
22/46
Conclusions
BOLD MRI could be a valuable method to
discriminate between AR and ATN by
measuring tissue oxygen bioavailability in
early kidney allograft dysfunction.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
23/46
chronic allograft nephropathy
loss of corticomedullary differentiation on R2*maps of patients with chronic allograftnephropathy with a decrease in medullary R2*
values that approaches cortical R2* values.These changes may reflect a decrease indeoxyhemoglobin in the medulla due todecreased tubular work and underutilization of
oxygen.Djamali A, Sadowski EA, Muehrer RJ, et al. BOLD-MRI assessment of intrarenal
oxygenation and oxidative stress in patients with chronic kidney allograftdysfunction.Am J Physiol Renal Physiol 2007; 292:F513F522
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
24/46
RENAL ARTERY STENOSIS
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
25/46
Juillard et al. found a graded increase in
cortical and medullary R2* value in response
to a decrease in renal blood flow in a pig
model.
decrease in cortical and medullary R2* value
with return to baseline values in response to
resolution of renal artery occlusion.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
26/46
BOLD MRI -evaluation of RAS in
humans.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
27/46
Furosemide was administered to examine the effect ofinhibiting energy-dependent electrolyte transport on
tissue oxygenation in subjects with renovasculardisease.
In 21 kidneys with normal nephrograms, administrationof furosemide led to a 20% decrease in medullary R2*
(P 0.01) and an 11.2% decrease in cortical R2*. In normal-size kidneys downstream of high-grade renal
arterial stenoses, R2* was elevated at baseline, but fellafter furosemide.
This finding suggests maintenance of functionalreserve in kidneys even in the presence of reducedGFR.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
28/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
29/46
However, atrophic kidneys distal to the totally
occluded renal arteries had a low R2* value
(or improved oxygenation) that did not
respond to furosemide challenge.
Thus, response to furosemide can serve as a
marker of maintained renal function in the
presence of RAS.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
30/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
31/46
Given the recent concerns with nephrogenicsystemic fibrosis (NSF) - use of contrastenhanced MRA and evaluation of GFR in
subjects with compromised renal functionneed additional caution.
Non-contrast methods, such as BOLD MRI,may provide important alternative techniques
for investigating vascular compromise andrenal functional status.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
32/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
33/46
Diabetic nephropathy
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
34/46
Using BOLD MRI, Ries et al. found significantly
lower oxygenation in the renal medulla of
diabetic rats than in a control group as early as
5 days after induction.
Epstein et al. found a significant increase in
oxygenation of the renal medulla in healthy
subjects in response to water diuresis. Thisresponse was absent in the diabetic patients.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
35/46
Epstein et al studied of eighteen human subjects(nine healthy non-diabetics and nine with mild,controlled diabetes)
In healthy subjects , water-diuresis led to a
significant increase in the oxygenation of therenal medulla, but not in the diabetic patients asevaluated by BOLD MRI.
These results suggest that even patients with
mild diabetes already show signs of renal injurylong before the onset of symptoms that usuallyaccompany kidney disease.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
36/46
Studies are being conducted to explore the
role of nitric oxide synthase and nitric oxide
inhibitors in animal models and diabetic
patients to better understand the role of nitricoxide in the pathogenesis of diabetes.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
37/46
Hypertension
Animal studies have shown that medullary
blood flow is decreased in hypertension and,
more importantly, that reduced medullary
blood flow is sufficient to produce
hypertension.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
38/46
Tempol (4-hydroxy-2,2,6,6-tetramethyl
peridinoyl) is a superoxide scavenger and is
known to improve NO bioavailability. Short- and long-term administration of tempol
has been shown to increase medullary blood
flow in hypertension rats by 35
50% andreduce mean arterial pressure (MAP) by 20
mmHg .
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
39/46
Tempol showed no effect on the R2* in
normal rats but significantly decreased in
hypertensive rats evaluated by BOLD MRI.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
40/46
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
41/46
Moreover, the complexity of the relationshipbetween renal oxygenation, severity of CKD, and
etiology of the underlying renal disease may require
that subjects be categorized not only by stage of CKD
but also by its underlying etiology.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
42/46
Limitations
BOLD signal intensity is an indirect marker of
renal oxygenation, and various factors
influence signal intensity on BOLD images.
These factors include oxygen supply and
consumption, blood flow, hematocrit, and
plasma oxygen (Po2).
Therefore, direct calibration of R2* valueversus Po2 is unreliable.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
43/46
The absolute magnitude of the R2* value is
less reliable in practice than the relative
changes observed in response to various
physiologic and pharmacologic challenges.
More work needs to be done to better
understand whether changes in BOLD signal
intensity in renal disease result from changesin oxygen supply or oxygen consumption
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
44/46
Summary
BOLD MRI is an endogenous contrast
mechanism and allows for rapid, noninvasive
means to assess intra-renal oxygenation in
humans.
Important applications in understanding renal
physiology and patho - physiology, and in turn
lead to the development of novelinterventional strategies.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
45/46
Identifying kidneys that maybe amenable to
functional recovery by restoring blood flow in
cases with renal artery stenosis
Distinguishing between acute rejection from
acute tubular necrosis in renal transplants.
Bold MRI imaging promises to become an
important tool for monitoring renaloxygenation in various clinical scenarios.
-
7/29/2019 BOLD (blood oxygen leveldependent) in nephrology
46/46