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Pulse Sequences and Acquisition Techniques for Breast MRI ACR Breast MRI Accreditation Program Launched May 2010 Ron Price Vanderbilt University Medical Center Nashville, TN 37232 Information available: www.acr.org Objectives Scientific Foundation of Current Breast MRI Protocols 1. Review basics of MRI breast cancer imaging 2. Present technical challenges of breast MRI 3. Advantages of specialized bi-lateral breast coils 4. Review typical pulse sequences for breast imaging 5. Discuss minimum technical requirements for pulse sequences for ACR accreditation 6. Discuss MRI acquisition protocols, sequence selection and data analysis 7. Present examples of breast MR images 8. Review approaches to image review and analysis Kuhl, et. al. Radiology 1999; 211: 101-110 2000 2005 2009 1

Kuhl, et.al. Radiology 1999; 211:101-110 Importance of Both Lesion Enhancement and the Enhancement Pattern Kuhl, et.al. Radiology 1999; 211:101-110 Continuous (likely benign) Suspicious (plateau) Highly Suspicious (washout) Degree of Enhancement Alone: Sensitivity: 91% Specificity: 37% Accuracy: 58% Both Enhancement and Curve Type Sensitivity: 91% Specificity: 83% Accuracy: 86% Group size: 266 cases, 101 cancers Still not perfect but much better. Challenges in Dynamic Contrast Enhanced Breast Imaging 1) Enhancing lesions result from Gd contrast agent leaking from poorly formed blood vessels within and around the malignant tumor. 2) The contrast agent shortens the T1 of the lesion relative to the surrounding normal tissues and thus may be detected as bright regions on T1-weighted images, provided there is adequate signal-to-noise (SNR). 3) The breast has significant adipose (fatty) tissues, also with short T1, thus create a significant background, fat-suppression is very important. 4) High 3D spatial resolution for small-lesion detection and shape assessment. 5) Enhancement patterns are critical to differentiation of benign and malignant masses, high temporal resolution is essential. 6) Full simultaneous coverage of both breasts is needed for comparison. 7) Image artifacts must be minimized: motion (cardiac and breathing), out-ofvolume wrap and non-uniform fat-suppression. Unfortunately: SNR, spatial resolution, volume coverage and imaging time all compete with one other and artifact free images may be difficult to obtain. An MR pulse sequence that can meet all of these technical requirements is a significant challenge. What is the appropriate spatial resolution and SNR? Basically, the answer is the best you can get and still maintain the necessary SNR and temporal sampling. The ACR guidelines have stated: 1) < 1.0mm X 1.0mm in-plane pixel size 2) < 3 mm slice thickness (with no slice-gap) 3) not too grainy Comparison: 1.25 X 1.25 mm pixel vs 0.6 X 0.8 pixels 1) Correctly upgraded BIRADS scores in 13 of 26 cancers 2) Correctly down-graded 10 of 28 benign lesions 2

How do we fat-suppress the images? Inversion Recovery (IR) Method 1) Short tau/ti inversion recovery (STIR) 2) Frequency selective saturation: (FATSat, CHEMSat, CHESS, PRESat) ) 3) Methods combining frequency selective and inversion recovery: SPIR (Spectral Presaturation with Inversion Recovery) SPAIR (Spectral Adiabatic Inversion Recovery) 4) Phase-cycling: (Dixon method, in-phase/out-of-phase using selected gradient-echo echo times) Uses null-point (M z = 0) of T1 recovery (Occurs at ~ 69% of tissue T1) Far at 1.5T: T1 ~ 250 msec Inversion time: TI ~ 160-170 msec (1.5 T) T1 T2 Fat 250 60 White Matter 700 75 CSF 2000 1000 5) Highly water-selective binomial RF excitation ( e.g. 1-3-3-1) RODEO* (Rotating Delivery of Excitation Off Resonance) *Harms,SE, et al Radiology 187: 493-501 (1994) Frequency Selective Fat Suppression Frequency-Selective Fat Suppression Pre-pulse 1) A 90 0 pulse centered at the fat frequency re-orients the fat protons into the transverse plane, in phase. The spoiling gradients are then used to destroy (crush or scramble) the coherence of the transverse magnetization to ensure that fat does not contribute to the image or 2) a SPAIR pre-pulse that is a 180 0 inverting pulse followed by a spoiler gradient. 1) Pre-pulse centered at fat resonant frequency with RFpulse bandwidth set for appropriate volume coverage 2) Nominal fat frequency located at 3.5 ppm below water frequency 3) Important to have homogeneous B0 field 4) B0 field will by affected by magnetic susceptibility of patient: Importance of good auto-shimming. RF G sl Fat-Sat pre-pulse Spoiler gradients RF excitation Slice Select gradient Gradient Echo Read Out G ro For: 1.5T = (64 X 10 6 Hz) X 3.5 pp/10 6 ~ 220 Hz G pe For: 3T ~ 440 Hz Phase Encoding gradients 3

What determines adequate temporal sampling? Enhancement Pattern for Focal Invasive Cancers (Type III Enhancement Curve) Adequate Temporal Sampling is Essential for Correct Enhancement Curve Classification Type III Type III MR Signal Time-to-peak enhancement ~ 1-3 minutes Type II? 0 1 2 3 4 5 6 7 (Minutes after contrast agent injection) 0 1 2 3 4 Temporal Sampling rate of >2 minutes (marginal for confident classification) 0 1 2 3 4 Temporal Sampling rate of 1 minute (accurate curve classification) Gadoliniun Contrast Agent: Rate and Volume 3D Fat-suppressed T1-weighted Gradient Echo Sequences (Most 3D sequences will use centric k-space filling.) 1) For accurate timing and consistency, power injector preferred 2) 0.1 mmol/kg (Typically, 10-20 ml volume) 3) Rate ~ 2 ml/s, w/saline flush MR Compatible Power Injectors General Electric Philips Siemens Aurora Hitachi Toshiba VIBRANT (Volume Image Breast Assessment) THRIVE (T1 High-Res Isotropic Vol Excitation) VIEWS (fl3d, 3D-FLASH) RODEO (1993, Harms and Flamig) TIGRE RADIANCE Typical Sequence Timing Parameters for T1-weighting: TE/TR/φ 1-3 ms/4-6 ms/10 0-15 0 Acquisition time: 1-3 minutes 4

Accurate temporal sampling requires specific knowledge of the 3D pulse sequence being used. How k-space determines image content Significance: Acquire center of k-space as contrast agent arrives to ensure maximum contrast enhancement. 1) Time of 3D gradient-echo volume acquisition (16-channel coil) 2) Method of k-space (spatial frequency) filling, e.g. sequential or centric. Note: May need to contact vendor representative for some of this information. Acquistiton time = TR X slice phase matrix X in-plane phase matrix X NSA Parallel Imaging Undersampling (Acceleration) Factors (SENSE, SMASH, GRAPPA...) Example: FOV = 250 mm, Matrix = 356 X 512 X 200 (SENSE) TE/TR/φ = 3.2 ms/6.5 ms/10 0 In-plane phase matrix = 356 (0.7mm X 0.7mm) Slice phase matrix = 200 (1-2 mm) SPAIR (Spectrally selective Adiabatic IR) Fat-suppression Acq. Time = 0.0065 sec X 200 X 356 2.8 (phase) X 2.0 (slice) = 83 sec Center - contrast Periphery - resolution Mezrich R, A Perspective on k- Space: Radiology 1995; 195:297-315 Paschal CB and Morris HD: k-space in the Clinic, JMRI 19(2) 145-159(2004) The center of k-space occurs when the zero-strength phase-encoding gradients are applied. For 3D phase encoding is applied in two directions: slice and in-plane phase. How do we achieve simultaneous coverage and good SNR? (0,0) Contrast Injection Scan Delay k-space center occurs at middle of scan Phantom Total Acquisition Time Small dedicated coils improve SNR by minimizing body noise Bi lateral coils allow simultaneous coverage. Multi channel (16) receive only coil arrays allow acceleration of acquisition times. Sequential k-space acquisition Power Injector Contrast Injection starts at k-space center (filled center to periphery) Scan Delay Acquisition Time Spiral or centric-elliptical (phase and slice) center-out for 3D k-space acquisition Feet first design for better patient acceptance. (bi lateral 7 channel array) Head first Interventional Coil and dedicated power injector 5

Benefit of dedicated receive-only breast coil arrays? 1) Dedicated small coils with FOV closely matching the volume of interest have reduced noise relative to large volume coils Noise is a function of the sensitive volume of the coil. For volume coils the entire FOV is contributing to noise. The limited sensitive volume of the surface coil has less noise and thus increased SNR. 2) Coil arrays allow reduced image acquisition times via parallel imaging Current bilateral breast coils may have 16+ parallel receive channels allowing undersampling (acceleration) factors as high as 6. *SENSE Imaging of the Breast, Friedman, et al: AJR (184), pp-448-451 (2005) SENSE* acceleration factor = 2 wth 8-coil array RF T1 Weighted 3D Fat Suppressed Gradient Echo Sequence (sequential, spiral or 3D elliptical k space filling) Fat suppression Pre pulse (e.g. SPAIR) G sl G ro G pe SPAIR Spoiler Centric-elliptic (phase and slice) α Slab selective RF pulse (10 0 15 0 ) TE (1-3 ms) TR (4-6 ms) Gradient Echo Phase Encoding (partition/slice) Read Out Sequential (e.g. bottom-to-top) Phase Encoding In plane Spoiler or Crusher gradients eliminate residual transverse magnetization and mimimizes T2 weighting. Sequences will run several un recorded cycles to establish equilibrium prior to acquisition. α Left MIP Coil-array sensitive volume must extend into chest wall. DCE pre-contrast Early post-contrast Non-uniform fat suppression Enhancing lesion Right MIP 5 mm lesion T2 (fat-suppression) Subtraction: post-pre Pre-contrast image Post-contrast image Subtraction image 3D Flash TE/TR/φ = 1.6 ms/4.4 ms/15 0 Slice thickness (DCE) = 1.0 mm TA = 86 sec FOV = 300X300 mm Matrix = 448 X 448 Pixel size = 0.7 X 0.7 mm Subtraction 6

Artifacts Good Temporal Sampling Essential for Kinetic Curve Characterization Phase-encode direction Patient Motion Out-of Volume Wrap-around Low-grade ductal carcinoma Rakow-Penner R, Hargreaves B, Glover G and Daniel B: Breast MRI at 3T, Applied Radiology pp 6-13, March (2009) Cardiac Motion Note: this is the correct PE direction to avoid breast overlap. Non-uniform fat suppression Review: Features of Breast DCE Protocol Recommended Breast MRI Protocol (Image acquisiton time ~15-20 minutes) 1. T1-sensitive pulse sequences and simultaneous bi-lateral breast coverage(3d Gradient Echo with shortest TE/TR) 2. High signal-to-noise coils (sensitivity) 3. High isotropic spatial resolution (less partial-volume/lesion detectability) 4. Fat suppression (background suppression/image contrast) 5. High temporal resolution (dynamic pattern definition) 1) Scout Images (~1 minute) 2) Pre-contrast (~5-7 minutes) i. T1-weighted no-fat suppression (fat/glandular morphology) ii. T2-weighted with fat suppression (bright fluid for cysts) iii. High-resolution, 3D T1-weighted fat-suppressed gradient-echo echo sequence (pre-contrast baseline image of identifying enhancing lesions) 3) Post-contrast (3-5 volume acquisitions ~ 10 minutes) Dynamic multi-phase 3D T1-weighted fat-suppressed GE sequence (Note: Pre-contrast and post-contrast images must have identical image paramaters to allow subtraction.) 4) Analysis i. Subtraction of pre-contrast and post-contrast images (identify enhancing lesions) ii. Dynamic contrast curve evaluation (enhancement pattern assessment) iii. Maximum Intensity Projection (MIP) images of subtracted images (vascular bed assessment) 7

ACR Accreditation Pulse Sequence Requirements www.acr.org CAD programs may improve consistency of breast MRI interpretation Breast MR Imaging: Computer Aided Evaluation Program for Discriminating Benign from Malignant Lesions, Williams TC, DeMartini WB, Partridge SC, Peacodk S and Lehman CD, Radiology: Vol 244 (1), pp-84-103 (2007) CAD program attempt to automatically identifies lesion by: 1)Enhancement threshold 2)Persistence of enhancement 3)Initial peak enhancement Commercial CAD systems are available through MR vendors. Conclusions 1. Automatic image subtraction 2. ROI time-intensity plot 3. Maximum Intensity Projection (MIP) images 4. Color coded overlay of suspicious enhancement patterns ROI 3D MIP Time-intensity plot Current imaging protocols for breast cancer assessment rely upon dynamic contrast enhanced (DCE) MRI to provide clearly detectable lesion enhancement as well as an accurate characterization of the lesion enhancement pattern. To meet these clinical i l requirements, the technical elements for breast MRI are: 1)A dedicated breast-coil array to provide high SNR images and simultaneous coverage of both breasts. 2)Fat-suppressed, T1-weighted 3D multi-phase gradient echo sequences with high in-plane spatial resolution (< 1mm X 1mm), thin slices (< 3mm) and good temporal resolution (~ 60sec) made possible by using parallel imaging. 3)Post-processing capability should provide post-contrast injection subtraction images, multi-phase time-intensity curves and maximum intensity projection (MIP) for 3D viewing and vascular maps. MIP Maximum Intensity Projection 8

Future: Kinetic Modeling for estimating Tumor extravasation rate constant: K trans Extravascular-extracellular volume fraction: V e DCE kinetic modeling for assessing breast cancer therapy response. Shift in K trans Distribution Following Therapy Pre-therapy 6-weeks of chemotherapy 9