MRI IN RADIATION TREATMENT PLANNING AND ASSESSMENT Yue Cao1 and Lili Chen2 Departments of Radiation Oncology and Radiology, University of Michigan1 Department of Radiation Oncology, Fox Chase Cancer Center2 Outline I. OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.2 Contrasts of MRI I.3 Radiographic Response I.4 Artifacts and Geometric distortions II. CURRENT MRI IN RADIATION TREATMENT PLANNING II.1 Target Definition II.2 Treatment planning and simulation II.2.1 MRI simulator II.2.2 Assessment and Correction for Geometric distortion II.2.3. Creation of MR DRR II.3 Use of MRI in place of CT for treatment planning III. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1 Physiological and metabolic MR techniques III.1.1 Diffusion MR technique III.1.2 Cerebral blood volume MR technique III.1.3 CBF MR technique III.1.4 Vascular permeability MR technique III.1.5 Proton MR spectroscopy III.2 Applications of physiological and metabolic MR in Radiation Oncology OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.1 Signal Source – Nuclear magnetic moments or spins of water protons – randomly oriented – lining up with a external magnetic field – precessing about the direction of B0 – Larmor relationship: ϖ0=γB0 – Magnetization: Longitudinal Mz=Mo Transverse Mxy=0 a b a) randomly oriented spins in a sample b) alignment of spins in a static magnetic field. OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.2 RF Excitation • Applying a small radiofrequency (RF) field of amplitude B1 to create the transverse magnetization Mxy • B1 oscillating at the Larmor frequency • B1 perpendicular to B0 • B1 rotates the magnetization away from B0 • The flip angle depends upon the amplitude and duration of B1 • Applying B1 long enough, the transverse magnetization will be equal to M0 B0 M0 M α Mxy OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.3 Free Induction Decay – Following a 90o RF pulse, M0 freely precesses about B0 – Inducing oscillating voltage in the receiver coil – Magnetization is decay due to the incoherent precessing frequencies of spins • Some of spins precess about B0 faster than others The envelope of the FID signals can be described as S=S0 exp(-t/T*2) OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.4 The Spin Echo • After a 90o RF pulse, spins start dephasing • Applying a 180o RF pulse τ seconds after the 90o pulse, the fast spins will be behind the low spins • Then, the spins will come back into phase with each other after another τ seconds. • The varying magnetic field induced in the receiver coil will form an echo, therefore it is called a spin echo. • The magnitude of spin echo – S= S0 exp( - TE/T2), TE=2τ • The amplitude of SE is decreased with an increase in TE due to incomplete refocuses of some of incoherent processes OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.5 T1 Relaxation Time • After FID or forming a SE, the magnetization eventually returns to its initial rest state (along B0) by a process called T1 or spin-lattice relaxation. – Two methods to measure T1 Saturation recovery S=S0 [1-exp(-t/T1)] Inversion recovery S=S0 [1-2 exp(-t/T1)] OVERVIEW OF MR IMAGING I.1 Principles of Magnetic Resonance Imaging I.1.6 2D Fourier Imaging Frequency gradient RF pulse time time Phase gradient Frequency encoding If a magnetic field gradient is applied along the x axis, the spins along the x axis will experience a differential magnetic field according to their position, rotate with different frequencies, and induce voltages with different oscillating frequencies in the receiver coils. Applying a onedimensional FT to the induced voltages will yield MR signals resolved along the x axis. Phase encoding If a gradient is applied along y axis for a short time period before recording the induced voltages, the spins along the y axis will have different phases due to that the spins that experience a larger field will rotate faster than the spins that are exposed to a smaller field. If this process is done N times and magnitude of y gradient-is different for each time, we will obtain N signals with N different phases. Again, applying a one-dimensional Fourier transform to the N signals with N different phases will yield the MR signals resolved along the y axis. time OVERVIEW OF MR IMAGING I.2 Basic MRI Contrasts – T1 weighted image • TE short, TR ~<T1 • Brighter for tissue w shorter T1 – T2 weighted image • TE ~<T2, TR long • Brighter for tissue w longer T2 – FLAIR T2 weighted image • Fluid-attenuation inversion recovery – Post Gd-DTPA T1 weighted image • Brighter for tissue that is uptake contrast – Contrast agent – Gd-DTPA • Shortening T1 Æ increase SI in T1WI • Shortening T2* or T2 Æ decrease SI in T2*WI or T2WI OVERVIEW OF MR IMAGING I.3 Treatment (radiographic) Response • Surrogate measure – Longest dimension, two longest dimensions, and volume of the tumor – 2000 NCI guideline • Longest dimension CR: disappearing tumor PR: decrease > 30% SD: increase <20% or decrease <30% PD: increase >20% or new lesions Pre Tx Post Tx OVERVIEW OF MR IMAGING I.4 Artifact and Geometric distortion • Artifact and geometric distortion – – – – – Inhomogeneity in the external magnetic field Inhomogeneity in the RF field any non-linearity and asymmetry in gradients Eddy currents a large change in magnetic susceptibility around tissue boundaries – Chemical shifts of water and fat – surgical clips and dental work – High field worse, fast sequences worse (EPI, GE, …) • Motion artifacts – Respiration motion – Cardiac motion – Involuntary motion CURRENT MRI IN RADIATION TREAMENT PLANNING II.1 Target Definition – Advantages of MRI • • • • Superior soft tissue contrasts Richness in various contrasts Widely available One stop to obtain anatomic, metabolic and functional images – Radiation treatment planning • Routinely used in brain tumor including primary and metastasis • Increasing its use in prostate cancer Å better delineation of prostate and rectal volume • a leaser extent in H/N, liver, pancreas, … CURRENT MRI IN RADIATION TREAMENT PLANNING ? CT Post-Gd T1W FLAIR CURRENT MRI IN RADIATION TREAMENT PLANNING II.2 Treatment planning and simulation II.2.1 MRI simulator – A system at FCCC • 0.23 T • Flat patient table top • 47 cm separation between two poles • Patient weight up to 400 lb A Philips 0.23 permanent magnet CURRENT MRI IN RADIATION TREAMENT PLANNING II.2 Treatment planning and simulation II.2.2 Assessment and Correction for Geometric distortion • Sources of geometric distortion – Hardware and software of the scanner – Patient induced • System dependent factors – Field strength: the lower field the less distortion – Filed of view: the smaller FOV the less distortion » The farther distance from the isocenter results in the large distortion CURRENT MRI IN RADIATION TREAMENT PLANNING II.2 Treatment planning and simulation II.2.2 Assessment and Correction for Geometric distortion • FCCC 0.23 system – 139 Hz/pixel in FE Æ insignificant distortion caused by chemical shifting and susceptibility – Distortion caused by imperfect gradient systems » Distortion of 2-3 mm if 12-18 cm is offset from the isocenter » Gradient distortion correction program Æ negligible distortion for the patient lateral size < 38 cm 7 mm distortion for the patient later size > 38 cm CURRENT MRI IN RADIATION TREAMENT PLANNING CT Uncorrected MRI GDC MRI CURRENT MRI IN RADIATION TREAMENT PLANNING II.3 Use of MRI in place of CT for treatment planning – II.2.3. Creation of MR DRR • Bony structures appear as signal voids on MRI • Bony structures can be contoured and assigned a bulk density – e.g., 2.0g/cm3 to pubic symphysis, femoral heads, acetabulum and sacrum for prostate patient – Accuracy of this method Æ 2-4 mm compared to CT DRR CURRENT MRI IN RADIATION TREAMENT PLANNING MRI-DRR CT-DRR CURRENT MRI IN RADIATION TREAMENT PLANNING II.3 Use of MRI in place of CT for treatment planning – gold standard • MR and CT image fusion with CT-based dose calculation – MRI-based treatment planning for prostate • Additional errors induced by the fusion process • substantial differences in bladder and rectal filling • redundant CT imaging session CURRENT MRI IN RADIATION TREAMENT PLANNING II.3 Use of MRI in place of CT for treatment planning – MRI-based treatment planning for prostate • Major concern: lack of electron density information for accurate dose calculation and heterogeneous anatomy • Several Monte Carlo studies have shown that there is no clinically significant difference in dose calculation between homogeneous and heterogeneous geometry for the pelvic region. • Adequate to use homogeneous density in prostate CURRENT MRI IN RADIATION TREAMENT PLANNING II.3 Use of MRI in place of CT for treatment planning – MRI-based treatment planning for prostate • Compared to the plan based upon CT and heterogeneous geometry for 15 plans – The mean differences: » <2.6% for isocenter dose » 1.25 ± 0.83 % for the maximum doses » 0.54 ± 0.4% for D95 of the PTV » 1.0± 0.49% for D17 of the rectum » 1.09 ± 0.31% D35 of the rectum » 0.96 ± 0.53% for D25 of the bladder » 0.66 ± 0.71% and D50 of the bladder CURRENT MRI IN RADIATION TREAMENT PLANNING 90% CT - based plan 100% 100% 90% MRI - based plan CT-based and MRI-based IMRT plans. The isodose lines are 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20% and 10%. CURRENT MRI IN RADIATION TREAMENT PLANNING 100 CT-based PTV MR-based PTV CT-based rectum MR-base rectum CT-based bladder MR-based bladder Volume (%) 80 60 40 20 0 0 10 20 30 40 50 Dose (Gy) 60 70 80 90 100 PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1 Physiological and metabolic MR techniques – Diffusion imaging – Diffusion tensor imaging – Vascular imaging including blood volume, blood flow, mean transit time, and vascular permeability – Metabolic imaging (1H, 31P, 13C, 19F,…) – Do not blindly use commercial software without evaluation (e.g., XXX) – Understand limitations of technologies PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1 Physiological and metabolic MR techniques III.1.1 Diffusion MR • The random motion of the water protons and the inhomogeneity of a magnetic field cause de-phasing of spins • Applying dephasing and refocused field gradients to sensitize an image to water proton motion • The diffusional signal loss by the gradient application is given – S=S0 exp(-bD) – large diffusion results in great in signal loss Low diffusion in tumor PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1 Physiological and metabolic MR techniques III.1.2 Cerebral blood volume and Cerebral blood flow MR techniques – Using DCE imaging, several vascular properties such as CBV, CBF, MTT(=CBV/CBF) and vascular permeability can be estimated. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS 1100 1000 900 S(t) III.1 Physiological and metabolic MR techniques III.1.2 Cerebral blood volume MR techniques – DCE T2* weighted images with an i.v. injected contrast bolus – An image volume can be acquired within 1-2 seconds – The acquisition continues for 1-2 minutes – The equation on the right hand side provides a good estimate of CBV – An overestimate or underestimate can occur in abnormal conditions 800 700 600 500 400 0 20 40 60 80 time (s) CBV ∝ ∫ ⎡ S0 ⎤ dt ln ⎢ ⎥ ⎣ S (t ) ⎦ PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1 Physiological and metabolic MR techniques III.1.2 Cerebral blood flow MR techniques – CBF can be estimated from DCE T2* weighted MRI and a artery input function AIF (t ) = 1 ⎡ S MCA0 ⎤ ln ⎢ ⎥ TE ⎣ S MCA (t ) ⎦ Tiss (t ) = ⎡ S ⎤ 1 ln ⎢ tiss 0 ⎥ TE ⎣ S tiss (t ) ⎦ t Tiss (t ) = ∫ AIF (τ ) R(t − τ ) dτ 0 – The residual function R is determined by deconvolusion computation (SVD) – The amplitude of the residual function R is proportional to blood flow. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS CBV CBF PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1.4 Vascular permeability MR technique Kin – Vascular permeability is estimated from T1weighted or T2* weighted DCE images and a compartmental model – Two compartmental model • Vascular space and extravascular extracellular space – Assumption ΔR1 =constant*C or ΔSI =constant*C blood inflow artery Kout capillary vein blood outflow extra-vascular space Two compartmental model t − k ( t −τ ) b Ct (t ) = K in ∫ e 0 C p (τ )dτ + v pC p (t ) PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1.4 Vascular permeability MR technique Vascular permeability images PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1.5 Proton MR spectroscopy – Proton MR spectroscopy (MRS) is a technique that is able to detect proton metabolites and chemical compounds in tissue – In an organic compound, electron bindings of each of protons with neighbor atoms are different, and generate a slight different but characteristic magnetic field offset. – Each of the protons in a compound has a slightly different resonance frequency even though the compound is immersed in the same external magnetic field. – Using this characteristic resonance frequency each proton can be uniquely identified on a spectrum, and the concentration of a compound can be estimated relatively to another compound. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.1.5 Proton MR spectroscopy – Chemical compounds and metabolites commonly detected in brain tissue • choline-containing compounds, creatine, lactate, lipid, and Nacetylaspartate (NAA) • Proton spectra can be obtained by 2D or 3D choline NAA PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology – Applications of physiological and metabolic MR in radiation therapy are emerging • • • • • Target definition Early prediction for treatment response Early prediction for treatment toxicity optimizing treatment strategies Endpoints – clinical, pathological, … PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology – Assessment for treatment response • A study of 28 patients with newly diagnosed GBM treated by fractionated radiotherapy and chemotherapy, the pre-radiotherapy volume of the metabolic abnormality (the region with choline/NAA > 2.5) within the T2 defined tumor volume predicted survival. PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology –Early assessment for treatment response • Another recent study of 23 high-grade gliomas found that the fractional tumor volume with high CBV prior to radiotherapy (RT) predicted survival fTV w High-CBV <0.07 P=0.002 fTV w High-CBV >0.07 (month) PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS Pre RT 1 week 3 weeks Subsequent decreases in the fractional tumor volumes with high-CBV at week 3 of RT were associated with better survival PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology – Early prediction for treatment toxicity • assessment of blood-brain or blood-tumor barrier opening in high-grade gliomas during radiation therapy using high-resolution post contrast MRI – A significant increase in the contrast uptake in the initially non-contrast enhanced portion of the tumor after ~30 Gy and up to 1 month post RT – A graduate decrease in the contrast uptake in the initially contrast enhanced portion of the tumor during RT PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS 12.00 Pre RT After ~30Gy Gd-DTPA Uptake Index 10.00 8.00 6.00 4.00 2.00 0.00 -2.00 pre-RT 1wk 3wk 1 mon pst 3 mon pst 6 mon pst PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology – Early prediction for hepatic venous perfusion dysfunction • Decreases in the regional portal vein perfusion one month post RT were predicted by the local doses and the decreases observed after received ~45 Gy in patients who underwent focal liver radiation • CT only allows us to acquire DCE images from a small slab (~2cm) of liver, but MRI allows to us to image the whole liver PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS 250 ml/100g/min 45 ml/100g/min 250 ml/100g/min 0 ml/100g/min 0 ml/100g/min 0 ml/100g/min Total perfusion Arterial perfusion Portal vein perfusion ΔFpv% 1 month after RT PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS ΔFpv% a fter 3 wee ks RT Gy) of RT in c d n (e e s o d Regional PHYSIOLOGICAL AND METABOLIC MR TECHNIQUES AND APPLICATIONS III.2 Applications of physiological and metabolic MR in Radiation Oncology – Early prediction for hepatic venous perfusion dysfunction • CT only allows us to acquire DCE images from a small slab (~2cm) of liver, but MRI allows to us to image the whole liver • Prediction of hepatic venous perfusion dysfunction post RT might have a significant impact on optimizing or re-optimizing radiation dose in individual patients SUMMARY • Roles of MRI in radiation oncology will continue increasing, including target definition for treatment planning, boost volume definition, early assessment for response, early prediction for radiation toxicity, and re-optimization for radiation treatment based upon normal tissue toxicity and tumor response. • Applications of physiological and metabolic MRI to RO will increase substantially.