1

Prof. Dr. Stefan O. SchoenbergProfessor and Chairman of Radiology

Department of Clinical Radiology and Nuclear MedicineUniversity Medicine Mannheim

Annual RSNA meeting, Chicago, 2009Annual RSNA meeting, Chicago, 2009

Renal artery disease:MR Techniques and Interpretation

1. To understand the basic technical principles of MR-Angiography with and without IV contrast agents, renal flow, perfusion and filtration measurements using magnetic resonance imaging (MRI)

2. To compare the various functional MRI techniques in terms of diagnostic value, complexity and clinical practicability

3. To demonstrate the added value of a comprehensive use of these techniques for assessment of different types of renovascular and renoparenchymal disease

Learning objectives

http://www.ikrn-mannheim.de/RSNA2009/renalMRtechniques.html

Background

N Engl J Med 2001; 344: 431-442

From macro- to microcirculation:technical possibilities of MRI

MRA

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0 100 200 300 400 500 600time [ms]

velo

city

[cm

/s]

Flow

Michaely HJ, et al. Abdominal Imaging 2006

Possibilities of MRIPerfusion

Oxygenation

Inflammation

Tissue structure

Dynamic MR-Urography

Possibilitiesof MRI

Dynamic MRA

Time-resolved Perfusion / Filtration / Excretion

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chw

indi

gke

it[c

m/s

]

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Plasma volume

Tubular volume

2

Parallel imaging, PAT ×2

26 s acquisition time, 0.9x0.9x0.9 mm

DSAMRA

Schoenberg SO et al. Radiology 2005; 235:687–698

Problem: eccentric stenoses

Voxel size: 3.4 0.7 mm3

y = 0.8208x + 6.0133R

2= 0.9087

y = 0.883x – 0.6697R

2= 0.7614

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Degree of area stenosis on IVUS [%]

Deg

ree

of a

rea

sten

osis

on

MR

A [%

]

20

Accuracy of high res. MRA vs. IVUS

Schoenberg SO et al. Radiology 2005; 235:687–698

FMD: PAT and 3T- a perfect marriage

25s>1.5mm³

19s1mm³

16s0.65mm³

1.5T, no PAT 1.5T, PAT 3 3.0T, PAT 3

Run-off MRA: renal artery findings

3T CTM MRA1.2 mm isotropic resolution0.1mmol/kg BW Gd-DOTA

SLE: Microaneurysms & systemic imaging

Inflammatory LNs Thick pericardium Pleural effusion

Flow: Cine phase-contrast flow measurements

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16 17 18 19 20

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dt)( ttGVV

time [ms]

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velo

city

[cm

/s]

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04/1997

1998

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08/1997

Right renal artery

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time [ms]

velo

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y[c

m/s

]

Apr 97Aug 9720002001

Re-stenosis

Schoenberg SO, et al. Abdom Imaging 2006; 31: 200-212

Grading scheme of renal artery stenosis

time [ms]0 200 400 600 800 1000

velo

city

[cm

/s]

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/s]

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grade 1 grade 2

grade 3 grade 4

Schoenberg SO, et al. JASN 2002, 13: 158-169

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15 125 235 345 455 565 675time [ms]

Vel

ocity

[cm

/s] Left renal artery

Right renal artery

DSA

Improved grading: MRA + PC Flow Post-interventional control of hemodynamics

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velo

city

[cm

/s]

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time [ms]0 200 400 600 800 1000

velo

city

[cm

/s]

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left

right

Schoenberg SO, et al. Radiologe 1997; 37: 651-662

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1 21 41 61 81 101 121 141

AU

ds/dt (maximum)

MTT

„MR-Renography“

Time [sec]

Time to Max

Dynamic renal perfusion with Gd chelates

Michaely HJ, Schoenberg SO. Radiology 2006; 238: 586-596

Postprocessing

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time in sec

sign

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time in sec

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First Pass Perfusion

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time in sec

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Filtration

+

t - 0s

t - 7s

t - 11s

t - 14s

t - 70s

t - 120s

4

1,5 Tesla 3 Tesla

Advantages of 3 Tesla for renal perfusion

1.5 Tesla 3.0 Tesla P-value

Baseline SNR kidney 9.6 ± 2.4 15.6 ± 5.3 p = 0.00005

Peak SNR kidney 60.1 ± 39.0 92.1 ± 38.7 p = 0.009

Michaely HJ,…, Schoenberg SO. Invest Radiology 2007; 42: 406-411

High-Grade RAS: MRA + Perfusion

60 y/o male with hypertension

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Signal [A.U.]

100

Right kidney

Renal artery aneurysm: decreased segmental perfusion

DSA

Segmental RAS: hemodynamic significance

30 y/o male with FMD perfusiondeficit at the lower pole of the kidney

Michaely HJ, Schoenberg SO. Radiology 2006; 238: 586-596

Maximum upslope (dS/dT)

5,250

2,182

Therapy Monitoring of RAS

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time [s]

sig

na

l in

ten

sity

[A

.U.]

after Stent

before Stent

before after PTA

Severe HTN with low-grade RAS

• 32 y/o female with severe HTN• RAS not significant• Biopsy: 2° nephrosclerosis0

20406080

100120140160180

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PatientNormal

5

Patient with glomerulonephritis

Normal MRA, abnormal perfusion study

Plasma flow (80ml/100ml/min)

Tubular flow (8ml/100ml/min)

Perfusion abnormal

Perfusion normal

MRAabnormal

MRAnormal

No renal disease

Renovascular diseasewith renoparenchymaldisease

Renovascular diseaseno renoparenchymaldisease

Renoparenchymaldisease

Selection of patients for intervention

Diagnostic Approach

FP < 100< 100ml/100ml/min

FP > 100> 100ml/100ml/min

94.7%100%58.1%Negative

predictive value

92.9%90%87.5%Positive predictive

value

90%85%90%Specificity

96.3%100%51.9%Sensitivity

either/orMRP-

positiveMRA-

positive

Detection of clinically significant renal disease

Attenberger UI et al. JMRI 2009,in press

350

0

188 ml/100ml/min

194 ml/100ml/min

Fibromuscular Dysplasia Chronic renal failure

Comprehensive assessment of renal disease

100

47 ml/100ml/min47 ml/100ml/min55 ml/100ml/min55 ml/100ml/min

0

• 60 y/o male S/P RTx 5 years agowith rise of serum creatinine

• No RAS

• Biopsy revealed chronic ischemia at the upper pole

Michaely HJ, Schoenberg SO. Radiology 2006; 238: 586-596

From macroFrom macro-- to microcirculationto microcirculation

28 ± 144 ± 114 ± 74 ± 468 ± 3446 ± 37Treated Tumors

5 ± 93 ± 382 ± 6015 ± 820 ± 6150 ± 89Untreated Tumors

12 ± 221 ± 7171 ± 5815 ± 415 ± 2188 ± 45Normal Kidneys

E [%]FE [ml/100ml/min]

FP [ml/100ml/min]

VP [ml/100ml]

TTP [s]MER [%]

Therapy Monitoring with MRI

Before Therapy

After Therapy

FP FE

Notohamiprodjo M,… Michaely HJ, JMRI 20009 in press

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Dynamic MRA at 3 T with PATDynamic MRA at 3 T with PAT

Michaely HJ, … Schoenberg SO, et al. J Magn Reson Imag 2006; 24: 1413–1419

13.5 ± 2.113.8 ± 1.7MTT [s]

10.2 ± 1.710.4 ± 1.3TTP [s]

TREAT@3,0T

TFL@1,5T

• Dynamic MRA (1.4 s temporal resolution) agrees with TurboFLASH for semi-quantitative perfusion measurements

• No significant differences for MTT and TTP between technique and field strength

Intravascular contrast agents (gadofosveset) @ 3 T:Time-resolved first pass (1.4 s temporal resolution)

Intravascular contrast agents (gadofosveset) @ 3 T:Time-resolved first pass (1.4 s temporal resolution)

Identification of target lesion

Measurement of area stenosis

Intravascular contrast agents (gadofosveset) @ 3T:Steady-State (0.9 x 0.9 x 0.9 mm)

Intravascular contrast agents (gadofosveset) @ 3T:Steady-State (0.9 x 0.9 x 0.9 mm)

CE-MRA, 1.1x1x1.2mm3 CE-MRA, 1.1x1x1.2mm3

Comprehensive protocols in the decade of NSF

Native-MRA (TrueFISP), 1x1x1mm³, 2-4min Native-MRA (TrueFISP), 1x1x1mm³, 2-4min

Non-contrast MRA: excellent in normal flow states

inconsistent results with low-flow

normal patient

Global Inversion and Readout

Selective Inversion and Readout after TI=1.2s

Subtraction of Images

Perfusion measurements with ASL (FAIR) ASL Perfusion – Improvement after therapy

• 56y/o female patient with right sided RAS (>70%)

• Affected left kidney shows reduced signal intensity

• After intervention the blood flow to the kidney is restored with signal intensity equal to the opposite side

9.2 5.50246

8101214

ASL-SNR

HealthySignificant RAS

Michaely HJ, Schoenberg SO, et al. Invest Radiol 2004; 39: 698-705

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Courtesy of Prasad PV, et al. Circulation 1996; 94:3271-3275

Intrarenal oxygenation by BOLD MRI

• Oxyhemoglobin is diamagnetic

• Deoxyhemoglobin is paramagnetic

• R2* (1=1/T2*) is directly proportional to the tissue content of deoxyhemoglobin

• A decrease in the slope implies an increase in the Po2

of blood

• Surrogate for medullaryperfusion

Effect of Water Diuresis On Relative Medullary Oxygenation

Pre

Pre

-- wa

ter

loa

dw

ate

r lo

ad

Po

st

Po

st --

wa

ter

loa

dw

ate

r lo

ad

AnatomicalAnatomical RR22* Map* Map

Courtesy of Prasad PV J J MagnMagn ResonReson Imaging 1997; 7: 1163Imaging 1997; 7: 1163--11651165

Changes in medullary pO2 post-waterload:Effect of endogenous prostaglandins

Courtesy of Prasad PV, et al. Kidney Int 1999; 55: 294-298

Perfusion: mean transit time R

340ml/min

Mean flow 340ml/minloss of early systolic peak

Mean flow 420ml/minnormal flow profile

T2* (BOLD): oxygenation R

Perfusion: plasma flow R

45 y old male with HTN and 50% stenosis R RA

pre PTA after 1st PTA after 2nd PTA

DSA pre and post PTA Plasma flow l > 200ml/min, r 70-90ml/min

Oxygenation (BOLD)

Tubular flow

Patient with FMD and spontaneous dissection

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a b c

Sadowski E et al, Radiology 2005

normal ATN Rejection

R2* loss – reflecting renal transplant rejection Threshold value for medullary R2* - 18/sec

Sadowski E et al, Radiology 2005

Relaxation times

Na H

Longitudinal relaxation T1 [ms] 301 9002

Transversal relaxation T2 [ms] 0.51 / 161 902

2311 1

1

1. Very short time of echo (TE)23Na:

T2s (60%)

T2F (40%)

0.0

0.2

0.4

0.6

20 40 Zeit [ms]

Amplitude

1 S. Nielles-Vallespin; PhD-thesis (2004)

2 Bernstein, King and Zhou: „Handbook of MRI Pulse Sequences“; Academic Press (2004)

Courtesy of Lothar Schad, PhD, CKM, Mannheim

Sodium Imaging

Maril N et al. (2006) Sodium MRI of the Human Kidney at 3 Tesla

3D gradient-echo sequence using an in-housebuilt quadrature surface coil with TR/TE 30/1.8 ms, FOV 38 x 38 x 24 cm3, and matrix128 x 128 x 16.

Water deprivation (12 hr) induced a significantincrease of 25% (P<0.05) in this gradient.

Magnetic Resonance in Medicine 56:1229-1234

Sodium Imaging

Healthy volunteer (5 x 5 x 5 mm3 )

Before water load After water load

Duration = 16 min; TE = 5,5ms; TR = 120ms; projections = 8000; flip angle = 85°

Sodium Imaging

Courtesy of Lothar Schad, PhD, CKM and Stefan Haneder MD, IKRN, Mannheim

Free diffusion

Restricted diffusion

Isotropy

Anisotropy

Structu

re

Analysis of tissue structure: Diffusion tensor ImagingAnalysis of tissue structure: Diffusion tensor Imaging

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Notohamiprodjo M et al. Invest Radiol 2008; 43: 677-685

RAS: measurement of fractional anisotropy

ADC left cortex << rightFA left cortex > rightFA left medulla >> right

ADC map

FA map

Signal change :-C: -65 %-OM: -62 %-IM: -60 %

T2*w MRI pre-USPIO T2*w MRI day 3 post-USPIO

• 53 yo male with purpura, acute renal insufficiency and proteinuria

Imaging of glomerulonephritis with USPIO

• Proliferative glomerulopathy with positive CD68 inflammatory cells (55/mm2)

USPIO Imaging of the kidneys

• Phase II study in 12 patients with renal biopsy as standard of reference

• USPIO – ultra small particles of iron oxide

• 1.7–2.6 mg Fe/kg KG (Sinerem®)

• T2* imaging before and 72h after USPIO administration

• For >5 macrophages/mm² mean signal decrease in renal cortex by 33±18%

• Detection of acute transplant rejection and ATN

T2* 72h after USPIO

T2* before USPIO

Acute tubular necrosis

(ATN) day 8 after renal TPx

Hauger O, et al. Eur Radiol 2007; 17: 2898-2907

1. MRA: spatial resolution <1mm3 for accurate stenosis quantification

2. Flow measurements for detection of hemodynamic significance

3. MRP for detection of renal parenchymal disease

4. Combined approach of MRA and MRP detection of clinically significant renal disease

5. NCE-MRA + ASL + BOLD allow (future) protocols without CM

6. USPIO for detection of inflammatory disease on a cellular level

Summary

http://www.ikrn-mannheim.de/RSNA2009/renalMRtechniques.html

Acknowledgment

• Department of Clinical Radiology and Nuclear Medicine, University Medicine Mannheim:Henrik J. Michaely MD, Ulrike I. Attenberger MD, Stefan Haneder MD, Steffen J. Diehl MD

• Department of computer-assisted clinical medicine (CKM):Lothar R. Schad PhD, Frank Zoellner PhD

• Department of Radiology, Evanston, University of Chicago:Pottumarthi V. Prasad PhD

• Department of Radiology, University of Bordeaux, France:Nicolas Grenier MD

http://www.ikrn-mannheim.de/RSNA2009/renalMRtechniques.html