Pottumarthi V. Prasad, Ph.D.Pottumarthi V. Prasad, Ph.D.Center for Advanced ImagingCenter for Advanced Imaging
NorthShore University HealthSystemNorthShore University HealthSystemEvanston, IL, USAEvanston, IL, USA
Diffusion & BOLD MRI of the kidney: a Diffusion & BOLD MRI of the kidney: a diagnostic and/or prognostic tool? diagnostic and/or prognostic tool?
Diffusion
Source: http://yihongs-research.blogspot.com/2008_01_01_archive.html,Source: http://physics.uoregon.edu/~raghu/TeachingFiles/Winter08Phys352/Notes_Diffusion.pdf
Simple Diffusion � Gaussian distribution
2
Diffusion Pulse SequenceDiffusion Pulse Sequence
−∆== −
3)(; 20
δγδgbeII bD
δδ
∆∆
gg
Diffusion MRI: Application to Acute StrokeDiffusion MRI: Application to Acute StrokeImaging @ 6 hrs
Diffusion MRI: Application to the KidneyDiffusion MRI: Application to the Kidney
RadiologyRadiology 1994; 193: 7111994; 193: 711--55
b=8 s/mmb=8 s/mm22 b=88 s/mmb=88 s/mm22
b=138 s/mmb=138 s/mm22 b=198 s/mmb=198 s/mm22
•• D ~ twice compared to most D ~ twice compared to most tissue, little difference tissue, little difference between cortex and medullabetween cortex and medulla
•• D measurements vary with D measurements vary with hydration statushydration status
Diffusion MRI of the Kidney: Effect of RAS & UODiffusion MRI of the Kidney: Effect of RAS & UO
RadiologyRadiology 1994; 193: 7111994; 193: 711--55RASRAS UUOUUO
b=0 s/mmb=0 s/mm22 b=800 s/mmb=800 s/mm22
Diffusion MRI: Renal MassesDiffusion MRI: Renal Masses
AJR AJR 2010; 194:4382010; 194:438––445445
Diffusion MRI: Healthy Diffusion MRI: Healthy vs.vs. CRFCRFHealthy, 13 yrs. old; ADC = 2.59 (Rt), 2.80 (Lt)
CRF, 73 yrs. old ; ADC = 0.88 (Rt), 0.83 (Lt)
JMRI 9:832 (1999)
ADC: Correlation with Cr ClearanceADC: Correlation with Cr Clearance
Radiol med (2007) 112:1201
Anisotropic Diffusion: Anisotropic Diffusion: Tracking White Matter FibersTracking White Matter Fibers
NMR Biomed. 2002;15:468–480
Anisotropic Diffusion MRI of the KidneyAnisotropic Diffusion MRI of the Kidney
Corte
xMed
ulla
Collecting System
Anisotropic Diffusion in the KidneyAnisotropic Diffusion in the Kidney
RadiologyRadiology 1994; 193: 7111994; 193: 711--55
Diffusion Tensor Imaging (DTI)Diffusion Tensor Imaging (DTI)
Magn Reson Imaging Clin N Am 16 (2008) 585–596
FA and ADC in Healthy SubjectsFA and ADC in Healthy Subjects
Medulla Cortex
Present study
FA 0.30 ± 0.02 0.23 ± 0.03ADC(×10-3 mm2/sec) 2.37 ± 0.14 2.56 ± 0.19
Ries et al.,2001
FA 0.39 ± 0.11 0.22 ± 0.12ADC(×10-3 mm2/sec) 2.30 ± 0.42 2.80 ± 0.32
Notohamiprodjo, et al., 2008
FA 0.36 ± 0.02 0.21 ± 0.03ADC(×10-3 mm2/sec) 2.16 ± 0.21 2.43 ± 0.19
T2W FA ADC
Lan Lu & Chris Flask, ISMRM 2010Lan Lu & Chris Flask, ISMRM 2010
Representative Maps for FA and ADCRepresentative Maps for FA and ADC
T2W FA ADC
eGFR >90(normal control)
eGFR = 76(DN Stage II)
eGFR = 32(DN Stage III)
Lan Lu & Chris Flask, ISMRM 2010Lan Lu & Chris Flask, ISMRM 2010
FA and ADCFA and ADC
*#
#
Medullary FA was significantly lower by ~25% in DN subjects.For control subjects, the FA in medulla was significantly higher than in cortex.
: P < 0.05 Control vs. DN;# : P < 0.05 Medulla vs. Cortex*
Lan Lu & Chris Flask, ISMRM 2010Lan Lu & Chris Flask, ISMRM 2010
Summary on Diffusion MRI of the KidneysSummary on Diffusion MRI of the Kidneys
•• Structure or Function Structure or Function –– controversialcontroversial•• Sensitive, but is it specific?Sensitive, but is it specific?•• Lack of standard acquisition protocolLack of standard acquisition protocol•• Advantages:Advantages:
–– NonNon--invasive allowing for longitudinal monitoringinvasive allowing for longitudinal monitoring–– TranslationalTranslational
•• Disadvantages:Disadvantages:–– No widespread availabilityNo widespread availability–– Complicated acquisition and analysis protocolsComplicated acquisition and analysis protocols–– Application to pediatric population not easyApplication to pediatric population not easy
Intra-renal Oxygenation
Franklin EpsteinFranklin Epstein
IntraIntra--renal Oxygenationrenal Oxygenation•• Based on arterioBased on arterio--venous difference, kidney venous difference, kidney as a whole has the least oxygen consumptionas a whole has the least oxygen consumption
Invasive Microprobe Measurements: Invasive Microprobe Measurements: Depiction of Regional ChangesDepiction of Regional Changes
FurosemideFurosemide AcetazolamideAcetazolamideAm J Physiol.Am J Physiol. 1994 Dec;267(6 Pt 2):F1059 1994 Dec;267(6 Pt 2):F1059
Invasive Microprobe MeasurementsInvasive Microprobe Measurements
�� Medullary OMedullary O22 consumption decreases consumption decreases Am J Physiol.Am J Physiol. 1994 Dec;267(6 Pt 2):F1059 1994 Dec;267(6 Pt 2):F1059
Oxygen ConsumptionOxygen Consumption
Adapted by permission from Macmillan Publishers Ltd: Kidney International, copyright 1997.
Need for regional rather than global measurementsNeed for regional rather than global measurements•• MR Imaging naturally provides regional measurementsMR Imaging naturally provides regional measurements
Kidney: a single organ?Kidney: a single organ?
NEJM NEJM 1995; 332: 6471995; 332: 647--5555
Invasive Microprobe MeasurementsInvasive Microprobe Measurements
FurosemideFurosemide AcetazolamideAcetazolamideAm J Physiol.Am J Physiol. 1994 Dec;267(6 Pt 2):F1059 1994 Dec;267(6 Pt 2):F1059
Medullary HypoxiaMedullary Hypoxia
NEJM NEJM 1995; 332: 6471995; 332: 647--5555
Oxy Vs. Deoxy Hemoglobin
Oxyhemoglobin DeoxyhemoglobinPARAMAGNETIC DIAMAGNETIC
(Similar to tissue )
BOLD MRI: Blood Oxygenation Level Dependent MRI
Ratio of Oxy to Deoxy hemoglobin depends on blood flow and oxygen consumption
BOLD Contrast: SimulationBOLD Contrast: Simulation
Courtesy: Todd Parrish, Northwestern Univ.Courtesy: Todd Parrish, Northwestern Univ.
BOLD MRI: Proof of PrincipleBOLD MRI: Proof of Principle
Prasad et al, Circulation 1996; 94: 3271
Post-furosemide
TE=29 ms
TE=50 ms
TE=80 ms
TE=100 ms
Prasad et al, Circulation 1996; 94: 3271
BOLD MRI: Changes BOLD MRI: Changes After Furosemide After Furosemide
BOLD MRI Changes with Tissue pOBOLD MRI Changes with Tissue pO22R2* = slope ~ deoxyHb ~ blood pO2 ~ tissue pO2
Prasad Prasad et alet al, , CirculationCirculation, 94, 3271 (1996), 94, 3271 (1996)
IncreasedpO2
Ln
(Inten
sity)
Echo Time (TE)
BOLD MRI: Effect of Furosemide BOLD MRI: Effect of Furosemide
Prasad et al, Circulation 1996; 94: 3271(n=6) (n=6)
Chan
ge in
R2*
(1/s)
Furosemide Acetazolamide0
2
4
6
8
10MedullaCortex
P < 0.01
NS
NS
NS
BOLD MRI: Uniquely Suited for Renal MedullaBOLD MRI: Uniquely Suited for Renal Medulla
With Furosemide, Medullary pO2 approaches that of the cortexBrezis et al, Am J Physiol 1994
Medulla
Cortex
Medulla
Cortex
RR22* Mapping:* Mapping:
2
50
50
2
Medulla
Cortex
Higher R2* in the medulla implies lower oxygenation.
Reduced R2* in the medulla implies improved oxygenation
Anatomy of kidney
Pre – furosemideR2* map
post – furosemideR2* map
BOLD MRI: BOLD MRI: In vivoIn vivo measurements in humansmeasurements in humans
Invest Radiol.Invest Radiol. 2006 Feb;41(2):181 2006 Feb;41(2):181
Tumkur S et al., Kidney Intl. 2006
Effect of Endogenous Prostaglandins
Pre-treated with Naproxen
BOLD MRI: Ureteral ObstructionBOLD MRI: Ureteral Obstruction
Radiology 2008; 247:754–761
BOLD MRI: RASBOLD MRI: RAS
Textor SCTextor SC et al, JASNet al, JASN 20082008
Normal Function ATN Rejection
BOLD MRI in Renal AllograftsBOLD MRI in Renal Allografts
Sadowski E, Fain S, UW, MadisonRadiology Radiology 2005; 236:9112005; 236:911––919919
Nl function vs ATN: P = 0.15ATN vs rejection: P = <0.001Nl function vs rejection: P = <0.001(two sample t-test)
23.9/s
n = 621.5/s
n = 615.9/s
n = 11
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
1
MED
ULLA
RY R
2* (1/s
)
Normal ATN RejectionFunction
Can BOLD determine cellular Can BOLD determine cellular vs.vs. humoral rejection and avoid biopsy?humoral rejection and avoid biopsy?
Banff IA = cellularBanff IIA = humoral (vasculitis)
18.0/s
n = 6 14.6/s
n = 5
0
2
4
6
8
10
12
14
16
18
20
1
MED
ULLA
RY R
2* (1/s
)
Type IA Type IIA
BOLD MRI in Renal AllograftsBOLD MRI in Renal Allografts
Summary on BOLD MRI of the KidneysSummary on BOLD MRI of the Kidneys•• Advantages:Advantages:
–– NonNon--invasive allowing for longitudinal monitoringinvasive allowing for longitudinal monitoring–– Combined with suitable pharmacological/physiological Combined with suitable pharmacological/physiological stimuli provide unique functional imaging capabilitystimuli provide unique functional imaging capability
–– TranslationalTranslational•• Disadvantages:Disadvantages:
–– No widespread availability of MRINo widespread availability of MRI–– Application to pediatric population not easyApplication to pediatric population not easy–– Cannot separate oxygen supply Cannot separate oxygen supply vsvs. consumption changes. consumption changes–– Not direct measure of pONot direct measure of pO22
diagnostic and/or prognostic tool?diagnostic and/or prognostic tool?
Radiology 247: 595-6 (2008)
Radiology Jun 2010
PrePre--clinical Models: UUO Modelclinical Models: UUO Model
Proc. ISMRM 2009: 668; Radiology Jun 2010Proc. ISMRM 2009: 668; Radiology Jun 2010
FibroblastFibroblastproliferationproliferation
UUO: Effects of ReversalUUO: Effects of Reversal
J Am Soc Nephrol 16: 3623–3630, 2005
1010--d UUOd UUO 22--wk after reversalwk after reversalContralateralContralateral
H & E stainingH & E staining
almost complete ablation of the outer renal medulla (arrow) as well as thinning of the renal cortex.
the cortexand the medulla show restoration of renal parenchyma
PrePre--clinical Models: rUUO Modelclinical Models: rUUO Model
Am J Physiol Renal Physiol 298:1024, 2010
Chronic Kidney Disease (CKD)Chronic Kidney Disease (CKD)• loss of peritubular capillaries (A),• decreased oxygen diffusion from
peritubular capillaries to tubular and interstitial cells of the kidney (B),
• stagnation of peritubular capillary blood flow induced by sclerosis of glomeruli (C),
• decreased blood flow as a result of imbalance of vasoactive substances (D),
• Inappropriate energy usage as a result of uncoupling of mitochondrial respiration induced by oxidative stress (E),
• increased metabolic demands of tubular cells (F),
• and decreased oxygen delivery as a result of anemia (G).
Semin Nephrol. Jul 2006;26(4):261-268
Preliminary Experience @ NorthShore Preliminary Experience @ NorthShore Longitudinal ChangesLongitudinal Changes
10 day rUUO10 day rUUO 28 day rUUO28 day rUUOAn
atomy
Anato
myRR 22
* Map
* Map
Preliminary Experience @ NorthShore Preliminary Experience @ NorthShore Longitudinal Changes Longitudinal Changes -- ADCADC
28 da
y rUU
O28
day r
UUO
10 da
y rUU
O10
day r
UUO
Preliminary Experience @ NorthShorePreliminary Experience @ NorthShoreCrossCross--sectional Data in Humanssectional Data in Humans
HealthyHealthyCKDCKD
Pre
Pre --La
sixLa
sixPo
stPo
st -- Las
ixLa
six
Stage 3Stage 3 Stage 5Stage 5
Quantitative RQuantitative R22* Measurements* MeasurementsRR22* (s* (s--11))
PrePre--furosemidefurosemide PostPost--furosemidefurosemide
CortexCortex MedullaMedulla CortexCortex MedullaMedulla
HealthyHealthy 20.620.6 41.341.3 23.423.4 25.525.5
Stage 3Stage 3 22.222.2 102.8102.8 15.515.5 67.367.3
Stage 5Stage 5 17.017.0 18.618.6 16.3516.35 17.017.0
Preliminary Experience @ NorthShorePreliminary Experience @ NorthShoreHealthyHealthy CKDCKD
DWI
DWI
ADCADCStage 3Stage 3 Stage 5Stage 5
ADC = 2.03 mmADC = 2.03 mm22/s/s ADC = 1.77 mmADC = 1.77 mm22/s/s ADC = 2.53 mmADC = 2.53 mm22/s/s
Thank you for your attention
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