Renal artery disease: MR Techniques and Interpretation Prof. Dr. Stefan O. Schoenberg Professor and Chairman of Radiology Department of Clinical Radiology and Nuclear Medicine University Medicine Mannheim www.ikrn.de Annual RSNA meeting, Chicago, 21 Learning objectives 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 www.ikrn.de/rsna21
Background N Engl J Med 21; 344: 431-442 From macro- to microcirculation: technical possibilities of MRI MRA Flow velocity [cm/s] 35 3 25 2 15 1 5 1 2 3 4 5 6 time [ms] Michaely HJ, et al. Abdominal Imaging 26
Potential of MRI Perfusion Oxygenation Inflammation Tissue structure Problem: eccentric stenoses MR A DSA Voxel size: 3.4.7 mm 3 Parallel imaging, PAT 2 26 s acquisition time,.9x.9x.9 mm Schoenberg SO et al. Radiology 25; 235:687 698
Accuracy of high resolution MRA vs. IVUS 1 Degree of area stenosis on MRA [%] 9 8 7 6 5 4 3 2 1 y =.828x + 6.133 R 2 =.987 y =.883x.6697 R 2 =.7614 2 3 4 5 6 7 8 9 1 Degree of area stenosis on IVUS [%] Schoenberg SO et al. Radiology 25; 235:687 698 PAT and 3 Tesla: a perfect marriage 1.5T 25s, no PAT >1.5mm³ 1.5T 19s, PAT 2 1mm³ 3T 16s, PAT 3.65mm³ Michaely HJ et al. Mag Res Clin N Am, 27
Run-off MRA: renal artery findings 3T CTM MRA 1.2 mm isotropic resolution.1mmol/kg BW Gd-DOTA SLE: Microaneurysms & systemic imaging Inflammatory LNs Thick pericardium Pleural effusion
Cine phase-contrast flow measurements 5 45 1 2 3 4 5 4 velocity [cm/s] 35 3 25 2 15 1 6 7 8 9 1 11 12 13 14 15 16 17 18 19 2 5 V V G t) ( tdt 21 22 23 24 25 2 4 6 8 1 12 time [ms] 4/1997 Re-stenosis 8/1997 35 3 25 Right renal artery Apr 97 Aug 97 2 21 1998 2 velocity [cm/s] 2 15 1 5 21 2 4 6 8 1 12 time [ms] Schoenberg SO, et al. Abdom Imaging 26; 31: 2
Grading scheme of renal artery stenosis 35 3 grade 1 35 3 grade 2 velocity [cm/s] 25 2 15 1 velocity [cm/s] 25 2 15 1 5 5 2 4 6 8 1 35 3 time [ms] grade 3 2 4 6 8 1 time [ms] 35 3 grade 4 velocity [cm/s] 25 2 15 1 velocity [cm/s] 25 2 15 1 5 5 2 4 6 8 1 2 4 6 8 1 time [ms] time [ms] Schoenberg SO, et al. JASN 22, 13: 158-169 Improved grading: MRA + PC Flow 6 Velocity [cm/s] 5 4 3 2 Left renal artery Right renal artery 1 15 125 235 345 455 565 675 time [ms] DSA
Post-interventional control Schoenberg SO, et al. Radiologe 1997; 37: 651-662 left velocity [cm/s] right velocity [cm/s] 45 preoperative postoperative 4 35 3 25 2 15 1 5 2 4 6 8 1 45 4 35 3 25 2 15 1 5 2 4 6 8 1 time [ms] New functional methods without contrast media Δ p = 8.4mmHg Visual assessment of PC VIPR magnitude images vs. DSA Visualization of flow physiology utilizing time-resolved phase information Courtesy PD Dr. T. Bley, University of Wisconsin
Dynamic renal perfusion with Gd chelates 16 ds/dt (maximum) MR-Renography A.U. 14 12 1 8 6 4 2 MTT 1 21 41 61 81 11 121 141-2 Time [s] Time to Max Michaely HJ, Schoenberg SO, et al. Radiology 26; 238: 586-596 Post-processing t - s t - 14s t - 7s t - 7s t - 11s t - 12s 7 Signal [a.u.] 6 7 6 5 5 4 4 3 3 2 1 2 1 5 1 15 time in s Signal [a.u.] + First Pass Perfusion 5 1 Signal [a.u.] 7 6 5 4 3 2 1 5 1 15 time in s Filtration time in s
Advantages of 3 Tesla for renal perfusion 1.5 Tesla 3 Tesla 1.5 Tesla 3. Tesla P-value Baseline SNR kidney 9.6 ± 2.4 15.6 ± 5.3 p =.5 Peak SNR kidney 6.1 ± 39. 92.1 ± 38.7 p =.9 Michaely HJ,, Schoenberg SO. Invest Radiology 27; 42: 46-411 A B C D
RAS: therapy monitoring with MRI Signal intensity [a.u.] Before PTA After PTA 8 y o female with arterial HTN before and after PTA before after PTA Michaely HJ et al, Abdom Imag 26 Severe HTN with low-grade RAS 18 16 14 12 1 8 6 4 Patient 2 Normal 25 5 75 1 32 y/o female with severe HTN RAS not significant Biopsy: 2 nephrosclerosis
Patient with glomerulonephritis Plasma flow (8ml/1ml/min) Tubular flow (8ml/1ml/min) Normal MRA, abnormal perfusion study Comprehensive assessment of renal disease 35 194 ml/1ml/min 1 188 ml/1ml/min 47 ml/1ml/min 55 ml/1ml/min Fibromuscular Dysplasia Chronic renal failure
Algorithm for differentiation of renal disease with functional MRI Strategy MRA + MRP + MRA ± MRP AUC.79.925.931 Exclusion of fixed renal damage (e.g. fibrosis) with new MRI techniques (e.g. DTI) Attenberger UI,, Michaely HJ, JMRI 29 From macro- to microcirculation 6 y/o male S/P RTx 5 years ago with rise of serum creatinine No RAS Biopsy revealed chronic ischemia at the upper pole Michaely HJ, Schoenberg SO. Radiology 26; 238: 586-596
New EMEA-guidelines (Nov 29) High-Risk Medium-Risk Low-Risk GFR < 3ml/min GFR 3-6ml/min Children, LTx Determination SCr Omniscan, Optimark, Magnevist and Generics Forbidden Dose minimization Forbidden Mandatory Multihance, Primovist, Vasovist Dotarem, Prohance, Gadovist Dose minimization* Recommended *single dose, no repetition within 7 days The GRIP Study Gadovist in Renally Impaired Patients prospective international study with > 3 patients included enrollment planned for 1 patients with CRF IV or V
Comprehensive protocols in the decade of NSF normal patient Native-MRA (TrueFISP), CE-MRA, 1x1x1mm³, 1.1x1x1.2mm 2-4min 3 Native-MRA (TrueFISP), CE-MRA, 1x1x1mm³, 1.1x1x1.2mm 2-4min 3 Non-contrast MRA: excellent in normal flow states inconsistent results with low-flow Perfusion measurements with ASL (FAIR) Global Inversion and Readout Selective Inversion and Readout after TI=1.2s Subtraction of Images
ASL Perfusion Improvement after therapy 56y/o female patient with right sided RAS (>7%) 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 14 12 1 8 6 4 2 Michaely HJ, Schoenberg SO, et al. Invest Radiol 24; 39: 698-75 9.2 5.5 ASL-SNR Healthy Significant RAS Intrarenal oxygenation by BOLD MRI Oxyhemoglobin is diamagnetic Deoxyhemoglobin is paramagnetic R 2 * (1=1/T 2 *) is directly proportional to the tissue content of deoxyhemoglobin A decrease in the slope implies an increase in the Po 2 of blood Surrogate for medullary perfusion Disadvantage: Confounded by blood flow and hemoglobin concentration Prasad PV, et al. Circulation 1996; 94:3271-3275
Post Post-water load Effect of Water Diuresis On Relative Medullary Oxygenation Anatomical R 2 * Map * Map Pre-water load Prasad PV et al. JMRI 1997; 7: 1163-1165 Impact of hydration 9 8 Increased blood flow oxygen availability Filtration oxygen consumption 7 6 5 4 Rebound Medulla T2*(ms) Medulla R2* (s-1) Cortex T2* Cortex R2* 3 2 1 prä_18:28: post 18:42: 18:47 18:52 18:57 19:2 19:7 time
Changes in medullary po2 post-waterload: Effect of endogenous prostaglandins Prasad PV, et al. Kidney Int 1999; 55: 294-298 45 y old male with HTN and 5% stenosis R RA Perfusion: mean transit time R Perfusion: plasma flow R Mean flow 34ml/min loss of early systolic peak Mean flow 42ml/min normal flow profile T2* (BOLD): oxygenation R
Quantification of therapeutic response after renal stent placement Pre-Therapy Post-Therapy Pre-Therapy Post-Therapy PF ml/1ml/min BOLD R2* loss reflecting renal transplant rejection a b c normal ATN Rejection Sadowski E et al, Radiology 25
Threshold value for medullary R2* - 18/sec Medulla Cortex Sadowski E et al, Radiology 25 Sodium MRI with 23 Na at 3 T Maril N et al. (26) Sodium MRI of the Human Kidney at 3 Tesla 3D gradient-echo sequence using an inhousebuilt quadrature surface coil with TR/TE 3/1.8 ms, FOV 38 x 38 x 24 cm 3, and matrix 128 x 128 x 16. Magnetic Resonance in Medicine 56:1229-1234 Water deprivation (12 hr) induced a significant increase of 25% (P<.5) in this gradient.
Sodium MRI with 23 Na at 3 T Healthy volunteer (5 x 5 x 5 mm 3 ) Before water load After water load Duration = 16 min; TE = 5,5ms; TR = 12ms; projections = 8; flip angle = 85 Courtesy of Lothar Schad, PhD, CKM and Stefan Haneder MD, IKRN, Mannheim Imaging of inflammatory renal disease ultra small particles of iron oxide (USPIO) Signal changes : -C: -65 % -OM: -62 % -IM: -6 % T2*w MRI pre-uspio T2*w MRI 3 days post-uspio 53 y o male with purpura, acute renal insufficiency and proteinuria 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 Acute tubular necrosis (ATN) day 8 after renal TPx T2* before USPIO T2* 72h after USPIO Hauger O, et al. Eur Radiol 27; 17: 2898-297 USPIO (P94) parenchymal changes Normal Ischemia-Reperfusion CyA-Toxicity In the rat model
Diffusion-Weighted Imaging (DWI) Diffusion-Tensor Imaging (DTI) Free diffusion Low cell density, free water motion in the interstitial room high ADC / isotropy Restricted diffusion High cell density, decreased water motion in the interstitial room low ADC / anisotropy Koh et al. AJR 27 DWI as a contrast media substitute? ADC values dependent on stage of CKD, not age Study with 72 volunteers and 43 patients, b=, b=5, 1.5T Xu X et al., Eur Radiol 21
DWI for evaluation of renal fibrosis 7T animal scanner DWI b-values 35, 6, 8, 1, 12 sec/mm² α-sma (smoot muscle actin), cell density Togamu O et al., Radiology 21 RAS: measurement of fractional anisotropy FA map ADC map ADC the left cortex << right FA left cortex > right FA left medulla >> right Notohamiprodjo M et al. Invest Radiol 28; 43: 677-685
Conclusion 1. MRA: spatial resolution <1mm3 for accurate stenosis quantification 3 Tesla new standard 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 Patient selection for intervention based on functional information 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 www.ikrn.de/rsna21