Respiratory Motion Prediction for Renal Perfusion MRI

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Respiratory Motion Prediction for Renal Perfusion MRI Presented by H. Michael Gach, Ph.D. Associate Professor of Radiology & Bioengineering University of Pittsburgh August 9, 2013

Agenda Overview of Renal Hemodynamics Perfusion MRI Techniques Free-breathing Perfusion MRI of the Abdomen

Renal Hemodynamics Arterial velocities - Descending aorta: 14 (0-75) cm/s - Renal arteries: 30-100 cm/s - Doppler ultrasound or phase contrast Cine MRI Renal blood flow (RBF): 1.1 L/min (22% of total blood flow). - ~10% of blood flow is filtered by glomeruli (GFR: 125 ml/min) - Gold standard p-aminohippurate (C PAH ) - invasive. - Ultrasound vascular resistance Renal perfusion: 250-500 ml/100g-min for cortex, 50-100 ml/100gmin for medulla - Radiotracer techniques (H 2 15 O, 133 Xe) - Contrast ultrasound - Contrast MRI methods P Martirosian et al., MRM 5: 353-361 (2004). http://web.squ.edu.om/med-lib/med_cd/e_cds/anesthesia/site/content/v03/030422r00.htm

Why Perfusion? Blood supply to the kidney indicates renal health and function. Transient/functional AKI results from decreased perfusion and may be rapidly reversible. Ischemic hypoxia initially impacts cortical metabolism. In renal transplant, cortical perfusion is significantly lower in acute rejection than acute tubular necrosis or normal allografts. Whole organ perfusion can be quantitatively measured noninvasively without risk to the kidney. Szolar et al., MRI 15(7):727-735 (1997). M. Le Dorze et al., Shock 37(4):360-365 (2012).

MRI Perfusion Techniques Intravascular Contrast (T 1 -wtd DCE or T 2 *-wtd DSC) - Uses injected Gadolinium chelates as exogenous tracer. - High signal changes (~50%) but high error (~50%) - Complicated tracer kinetics and deconvolution. - Difficult to obtain quantitative measurements. - Contraindicated for AKI, renal failure and impairment. Arterial Spin Labeling (ASL) - Uses blood water as endogenous tracer. - Small signal changes (~3%) but small error (~15%) - Tracer kinetics are simpler. - Absolute quantification may be possible. - Limitations with multi-slice acquisitions. - Subtraction technique (Control Label) is highly sensitive to motion. - Safe.

MRI ASL Perfusion Milestones 1992: Perfusion MRI with single-slice continuous arterial spin labeling (sscasl) first reported in animal (CMU). 1994: sscasl used in human brain to measure CBF (Penn). 1994: sscasl used to measure perfusion in rat kidneys (CMU). 1995: sscasl used in human kidneys (Penn). 1998: sscasl used in transplanted rat kidney (CMU). 2000: Multislice Pulsed arterial spin labeling (mmpasl) used in the human kidney. PubMed Citations for ASL 2004: PASL True-FISP in human kidney. 2005: PASL used in human RCC. 2005: pcasl is created, allowing high-field CASL.

PASL vs. CASL (Body Coil XMT) CASL: Arterial spins are continuously inverted as they travel through descending aorta, label decays on route to imaging volume. Label is created at fixed labeling plane. PASL: Fresh spins outside of the imaging volume flow into the imaging volume. The labeled imaging volume decays as spins move into it. Source of label is dispersed outside of the imaging volume. CASL PASL Tracer Labeling Plane Tracer Imaging Volume Imaging Volume PASL

Continuous Arterial Spin Labeling (CASL) CASL uses RF-based adiabatic fast passage to invert flowing blood water spins. Inverted spins flow into the tissue resulting in a small signal drop. B 0 Flow Flow Tissue Water Spins Blood Water Spins Labeling RF Field Artery Arterioles Venules Capillaries Vein +f

Adiabatic Fast Passage The adiabatic inversion efficiency can be modeled using: 1 e 2 B l 2G v G l - Labeling gradient B l - Labeling RF v - Spin velocity γ - Gyromagnetic ratio l G l = 1 mt/m Takeaway: The inversion efficiency decreases with higher arterial flow velocities. HM Gach et al., 2002, MRM 47(4):709-719.

CASL Signal Kinetics Labeling RF Transit Delay Image Control RF Transit Delay Image ~2 s ~1 s ~1 s ~2 s ~1 s ~1 s Arterial Input Function a(t) 1 0.8 0.6 0.4 0.2 Image Acquisition M C (t)-m L (t) M 0 (t) Transit Times (s) 0 0 2 4 6 8 10 Time (s) Relaxation Function m(t) 1 0.8 0.6 0.4 0.2 0 0 2 4 6 8 10 Time (s) Perfusion Rate 250 ml/100g-min α = 0.8

Respiratory Motion Coronal 3D Fast Gradient Recalled Echo (T 1 weighted) Free-Breathing Breathhold Navigator-Echo Gating

Renal Perfusion Images using SPDI CASL (w/ Breathholds) at 1.5 T Six Axial Slices (Control-Label) of Healthy Female Coronal Localizer

Real-Time Tracking Free-Breathing Navigator Motivation Physiologic motion of internal organs introduces unacceptable error in quantitative MRI/MRS studies (e.g., in abdomen and chest). Multiple or long (e.g., DSC) breathholds during long exams are too difficult for sick and most healthy subjects. Accurate and reproducible breathhold positioning (better than +/- 1 mm) is very difficult. Wasted scan time (i.e., deadtime) using gated navigators can exceed 50% of the scan time or worse for breathholds. Ideally, we want real-time data acquisition corrections without breathholds, deadtimes, or discarded acquisitions.

Respiratory Motion Superior Subject 1 Subject 2 Inferior 1.5 T MRI, Coronal EPI: 256x128, TR: 137 ms, FOV: 39 cm

Respiratory Motion Ratio Normal Respiration Deep Respiration Diaphragm S/I : R/L 6.0 +/- 1.9 8.8 +/- 3.8 S/I : A/P 5.1 +/- 1.9 5.0 +/- 2.7 Lung S/I : R/L 6.0 +/- 1.9 N/A S/I : A/P 5.1 +/- 1.9 N/A S/I: Superior/Inferior R/L: Right/Left A/P: Anterior/Posterior Human Motion Displacement Ratios Korin H.W. et al., Magn Reson Med, 1992. 23(1): p. 172-8.

Organ Respiratory Motion S/I Displacement Normal Respiration Mean (Range) Deep Respiration Mean (Range) Liver 2.5 (1-4) cm 5.5 (3-8) cm Pancreas 2.0 (1-3) cm 4.3 (2-8) cm Right Kidney 1.9 (1-4) cm 4.0 (2-7) cm Left Kidney 1.9 (1-4) cm 4.1 (2-7) cm Diaphragm 1.3 cm 3.9 cm Lung 1.0 (0.3-2.5) cm N/A Suramo I. et al. Acta Radiol Diagn (Stockh), 1984. 25(2): p. 129-31. Korin H.W. et al., Magn Reson Med, 1992. 23(1): p. 172-8.

Navigator Echo 2D Excitation (x-y) 1D Readout Direction (z) 1D Readout Direction Acceptance Window VS Deshpande and D Li. Current Protocols, June 2008

Navigator Options Excitation Readout Description Time 1D 1D B0 correction (e.g., in Siemens EPI readout) 2D or 2-1D's (SE) 1D 1D Translation (1D PACE) used for cardiac and respiratory gating 1D 2D 1D Translation (2D PACE) used for respiratory gating 1D or 2D 2D 2D In-plane: rotation and translations Non-Selective? 3D 3D: Rotations and translations (typically integrated into 3D pulse sequence readout). 1D 2D Multislice 3D: Rotations & translations (3D PACE). Reconstructed images used to prospectively correct subsequent acquisitions (e.g., fmri) ~1 ms ~30 ms >100 ms ~30 ms ~30 ms Depends on Image Acq. Time

Prospective Motion Correction (PMC) & Respiratory Motion Prediction (RMP) w/o Respiratory Motion Prediction (RMP) Imaging Plane ROI Body Body Body Navigator Acquired Image plane is shifted per ROI displacement Image is acquired as ROI moves out of imaging plane. w/ RMP Body Body Body Navigator Acquired Image plane position is predicted and shifted Image plane and ROI are aligned.

Motion Compensation Technique Patient Effort Scan Time Accuracy No Compensation Minimal Minimal ~ 5 cm Breathhold Very Difficult Medium ~ 1 cm Breathhold with respiratory Very Difficult Medium ~ 2-4 mm feedback display Navigator gating (narrow Minimal Long ~ 1-2 mm window) Navigator gating (wide window) Minimal Medium ~ 2-4 mm Navigator gating with respiratory feedback display Real-time tracking & prospective motion correction (PMC) Medium Medium ~ 1-2 mm Minimal Medium ~ 1 mm

Real-Time Tracking Navigator (1.5 T) No Motion Transverse Image Slice S/I Harmonic Motion (10 mm/s, 10 mm amplitude) Imaging Volume (Fixed) Superior Phantom Inferior Superior Imaging Volume (Dynamic) Phantom Inferior Time after Navigator 50 ms 500 ms Gach et al, ISMRM: 2990 (2006).

0 s 8 s 16 s 0 s 8 s 16 s 24 s 32 s 40 s 24 s 32 s 40 s 48 s 56 s 64 s Real-Time Tracking, Free-Breathing Navigator in Kidney 48 s 56 s 64 s Without Navigator correction CASL Perfusion Map Renal Cortex CASL at 1.5 T with single-shot spiral (64x64, FA:90 0, TE: 8 ms, TR: 8 s, 3.7 s label, 100 ms postlabel delay). Gach et al, ISMRM: 2990 (2006).

Prediction Theories Goal: Predict the future location X t>0 from samples acquired in the past X t<0 Approaches: Deterministic: Seek a true prediction. Stochastic: Location is a random variable. Seek to minimize variance.

Comparison of RMP Models Predictor Pre- Training Training/ Warm-Up Pros Cons Computational Cost Deterministic Linear Multiple Linear Not Required Not Required Yes Yes Simplicity Adaptive switching among multiple models Operates on single linear mode Inferior for long prediction in which active model switches Low Low Stochastic Kernal Density Estimator Local Circular Motion Yes Not Required Not Required Yes Flexible, almost constant with respect to prediction length Consistent performance with respect to sampling rate Computation, single point prediction Intrinsically local, degraded performance for long prediction High Low

Respiratory Motion Predictor (RMP) Model Training: Real-time Sampling & Analysis Operation: Periodic Sampling, Model Updating, & Prospective Compensation (if applicable) Navigator Excitations & Readouts, Navigator History Data Processing Motion Corrections & Prediction, Real-time Updates RMP Training (Scout) Label or Control RTT PMC Image Acquisition

Motion Compensation Objectives Accurately measure organ motion in real-time for both MRI and PET motion correction using: - Sufficient motion degrees of freedom. - Adequate sampling rates. - Accurate and efficient algorithms. Minimize image acquisition deadtimes associated with navigators. - Efficient MRI navigator design. - Motion prediction/extrapolation during image acquisitions from motion history and models. - Efficient PET/MR data integration for image reconstructions.

NIH Funded Research: Respiratory Motion Prediction (RMP) in pcasl Perfusion MRI of Clear Cell Renal Cell Carcinoma (ccrcc) 124 I-cG250 PET/CT of ccrcc (~10 s) pcasl MRI sequence Transit with RMP. (2 s) Delay (~ 1 s) (< 1 s) Navigator Scouts/ Model Training Label or Control Navigators/ Model Update & Prediction TR (~ 5 s) 2D or 3D Image Acquisition Navigators/ Model Update Label or Control...

Hybrid or Pure Image-Based RMP Two folds of image-base processing for improved accuracy: - Image volume in training: Build a motion manifold model: improves on the 1D or 3D point trajectory modeling. - During acquisition, combine navigator info (during transit delay) and acquired volumetric image information to update the manifold model and perform online prediction.

Improving the Prediction: Inference Training (Pre-Training) 1D Navigators 1D Navigators 1D Navigators 1D Navigators 2D or 3D Image Acquisition 2D or 3D Image Acquisition 2D or 3D Image Acquisition 2D or 3D Image Acquisition 1D Motion 3D Motion Inference Model Prediction Model

Non-Parametrically Reconstructed Motion Manifold (Voxel Based) Image Registration Motion Manifold Recon. Spatiotemporal behavior of the volume of interest (kidney in this example) Whole Domain Within Kidneys Motion Manifold Optical Flow Error (mm) in motion manifold characterization Mutual Information MAE Std. MAE Std MAE Std. W/o I.C. 4.87 2.16 2.61 2.37 2.60 1.78 With I.C. 4.92 2.13 7.61 3.80 7.76 5.53 W/o I.C. 4.34 1.81 5.68 3.98 2.56 1.20 With I.C. 4.33 1.81 8.89 4.64 8.15 3.54

Estimated Motion using Shape Contouring (Boundary-Based)

Respiratory Motion Prediction Algorithm Development SI motion (Diaphragm) in mm. 16 14 12 10 8 6 4 2 0-2 Weighted Fourier Linear Combiner Input Prediction after training Prediction during training 0 5 10 15 20 25 30 Time (secs) Training Ends Normalized root mean squared error Kernal Density vs. Adaptive Linear Model 10 Hz Sampling Rate Adaptive Linear Model Interacting Multiple Model Kernal Density Estimator Local Circular Motion Nair & Gach. ISMRM 4600 (2011). Hong et al., Phys Med Biol 56: 1775-1789 (2011).

Prediction Window: 0.2 s Comparison of Predictors Adaptive Linear Model (Linear) Interacting Multiple Model (MLM) Kernal Density Estimator (KDE) Local Circular Motion (LCM) Prediction Window: 0.6 s Prediction Window: 0.4 s Hong et al., Phys Med Biol 56: 1775-1789 (2011).

Benchmarking Dell T1500 workstation with 64-bit quad-core, 2.93 GHz running Linux Average computational time/prediction (μs) CV IMM WFLC MATLAB 106.2 342.5 4551.8 C++ 1.1 7.2 211.3 Nair & Gach. ISMRM 4600 (2011).

Status: Respiratory Motion Prediction Acquired human respiratory motion data and testing basic protocol. Began evaluating prediction algorithms using in vivo data in collaboration with Dan Ruan (UCLA). Integrated 1D navigator excitations into 2D EPI pcasl and 3D GRASE pcasl. Developing real-time feedback interface for receiving and processing navigator data, and predicting organ position.

Collaborators Respiratory Motion Predictor Hao Song (Pitt Radiology) Dan Ruan (UCLA, Radiation Oncology) Sungkyu Jung (Pitt Statistics) Xiang He (Pitt Radiology) Tejas Nair (GE) Original Sequences: Maria Fernandez Seara (FIMA, Univ. Navarra) Rolf Pohmann (Max Planck Institute) Siemens