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