Clinical applications of MRI in radiation therapy. Jatta Berberat, PhD Kantonsspital Aarau

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1 Clinical applications of MRI in radiation therapy Jatta Berberat, PhD Kantonsspital Aarau

2 Background and introduction Magnetic Resonance Imaging Relaxation mechanisms Imaging gradients FFT Basic sequences parameters SE GE IR Advanced techniques Volumetric imaging Artifacts Clinical applications of MRI in RTP GTV PTV OR Special MRI techniques used in RTP fmri DWI/DTI Introduction

3 Background and introduction

4 Magnetic Resonance Imaging Several advantages when compared to other imaging techniques: Safe and non-invasive Can be optimized to image specific tissues Can be used quantitatively Rapid development of devices will allow: higher and higher resolutions in future more rapid aqcuisitions

5 Nuclear Magnetic Resonance (NMR): Based on the interaction between external magnetic field (B 0 ) and the nucleus of an atom Only nucleons possessing spin-property react to the external magnetic field depends on its amount of protons and neutrons: Nuclei with an identical number of protons and neutrons = no spin Nuclei with an odd number of protons or an odd number of neutrons or both have an overall spin The nucleus studied in MRI is usually 1 H, water proton tissues consist mostly of water (60-80%) and fat 1 H is the most common isotope of hydrogen (about %)

6 Nucleus and magnetic field Rotating charge induces a magnetic field 1 H, hydrogen nucleus (proton) can be viewed as small bar magnet N S

7 Outside the magnetic field Protons without magnetic field are randomly orientated No orientational preference no net magnetization

8 Inside an external magnetic field B 0 A proton starts to precess inside the magnetic field N The rate of precession is the Larmor-frequency: B 0 S ω = γb 0 γ = MHz / T for 1 H, so-called gyromagnetic ratio

9 Inside the magnetic field, net magnetization will occur The magnetic dipolemoment = µ B 0 or: µ has the direction of the B 0 field The nucleus can have 2s + 1 energy stages: E = m s γħb 0 = m s γħω 0, where ms= s, s + 1,..., s 1, s and ħ is Dirac s constant 1 H has two possible energy levels: parallel (+1/2) or anti-parallel ( 1/2) state with respect to the static field The uneven distribution of the proton Populations is given by the Bolzmann equation N 1/2 /N +1/2 = e E/kT = e ħ ω 0 /kt

10 Inside the magnetic field, net magnetization will occur B 0 z y B 0 M z y x x net magnetization

11 Magnetic resonance Energy is applied as radiofrequency (RF) energy usually in so-called 90º and 180º pulses (SE) Rf-energy applied M M re-emitting the absorbed energy (FID) protons begin to realign themselves to the direction of main magnetic field

12 Relaxation Relaxation times characterize the behavior of magnetization after rf-pulses T 1 relaxation, spin-lattice or longitudinal relaxation (towards z axis) protons return to equilibrium by releasing their energy to surroundings lattice z xy

13 Relaxation T 2 relaxation, spin-spin or transverse relaxation (xy-plane) decrease of transverse coherence of protons energy is exchanged between spins sensitive to water mobility combination of magnetic field inhomogeneities and spin spin transverse relaxation, with the result of rapid loss in transverse magnetization and MRI signal=free Induction Decay (FID) T 2 * = total relaxation time T 2 = spin-spin relaxation T 2`= component of T 2 Relaxation time induced by field inhomogeneities

14 T 1 relaxation increase of longitudinal magnetization T 2 relaxation decrease of transverse magnetization M z M xy T 1 T 2 t or: t

15 T 1 relaxation increase of longitudinal magnetization T 2 relaxation decrease of transverse magnetization runners on track

16 Imaging

17 Gradients Three physical gradients: x, y and z gradients embedded inside magnet used to modify static magnetic field Gradients used in imaging Slice selection gradient (G SS ) Read-out or frequency encoding gradient (G RO ) Phase encoding gradient (G PE )

18 Slice selection gradient together with appropriate Rfpulse is used to select one slice The slice selection gradient G SS determinates both the slice thickness and the slice position. z 1 z 2 z 3 G ss f 1 f 2 f 3 Slice selection in MRI is the selection of spins in a plane through the object. Tissue located at position z i will absorb rf energy broadcasted with a central frequency f i. Each position will have a unique resonant frequency.

19 Once the slice is selected, (frequency) read out gradient G RO and phase encoding gradients G PE are used for spatial encoding G PE y 3 y2y1 p 1 p 2 p 3 Prior to application of G PE, all protons will precess at the same frequency The precessing frequency of the protons is dependent of the y i position Once G PE is turned off, the proton will precess at it s originally frequency. Phase shift is marked with p i.

20 The read out gradient G RO is perpendicular to the slice & pulse direction: x 1 x 2 x 3 In G RO encoding, each proton within the excited volume precesses at the same frequency f i. Frequency of the precession depends on its position x i. f 1 f 2 f 3

21 From this frequency and phase map, regular image can be calculated using Fourier Transform freq phase Each pixel in the image is related to the amount of spins and the magnetic environment at the corresponding location in the sample

22 K-space is an extension of the concept of Fourier space is a temporal memory of the spatial frequency information in two or three dimensions of an object is defined by the space covered by the phase and frequency encoding data In 2-D FT imaging, a line of data corresponds to the digitized MRI signal at a particular phase encoding level The position in k-space is directly related to the gradient across the object being imaged By changing the gradient over time, the k-space data are sampled in a trajectory through Fourier space at each point until it is filled. In SE every TR is one line on a k-space

23 Sequences

24 Spin Echo (SE) spin echo refers to the refocusing of precessing nuclear spin magnetisation by a 180 pulse of resonant radiofrequency. 90 RF pulse -> excitation pulse: rotates the magnetization M z into the xy-plane -> dephasing of the transverse magnetization (M xy ) starts 180 pulse -> refocuses the spins to generate signal echoes

25 Gradient Echo (GE) generated by using a pair of bipolar gradient pulses There is no refocusing 180 pulse data are sampled during a gradient echo: negatively pulsed gradient dephases the spins -> they are rephased by an opposite gradient with opposite polarity to generate the echo The echo is produced by reversing the direction of a magnetic filed gradient or by applying balanced pulses of magnetic field gradient before and after a refocusing RF pulse so as to cancel out the position dependent phase shifts that have accumulated due to the gradient. 1. exitation pulse 2. negative gradient is applied (rapid dephasing of transversal M) 3. Positive gradient is applied (reverses the magnetic field) 4. Spins begin to rephase forming a gradient echo

26 GE sequences GE short TR -> shorter acquisition time T1w GE GE image of a wrist artifacts in regions with varying susceptibility e.g. between the air-containing sinuses and brain especially between haemogghages and normal tissue

27 Inversion recovery (IR) T 1 in a given region can be calculated from the change in the MR signal from the region due to an inversion pulse with a different inversion time (TI) 180 RF pulse -> tilts the magnetization to z-direction -> rotates the magnetization M z into the negative plane After TI -> 90 RF pulse tilts some or all of the z-magnetization into the xyplane -> signal is rephased with a 180 pulse as in the SE sequence During the initial time period, various tissues relax with their intrinsic T 1 relaxation time provides very strong contrast between tissues having different T 1 relaxation times or to suppress tissues like fluid or fat - additional inversion RF pulse increases aqcuisition time TI

28 better T1-contrast Selective suppression" (FLAIR) IR sequences longer measurement time allows to choose less slices (acquisition time should be in clinical routines as short as possible) IR T1 STIR FLAIR

29 SE sequences long TR long TE T2: T 2 fat bright Liquid bright Could be used for: detection for abnormal fluids meniscal tear in knee (synovial fluid will be seen brighter than the cartilage) etc.

30 SE sequences T 1 T1: short TR short TE fat bright liquid dark used for: predicting pathology with oedema or a lot of capillaries fatty lesions clear boundaries between different tissues etc.

31 Contrast on SE images Parameters SI Short T 1 Long T 1 Short T 2 Long T 2 short PD long PD Short TE Long TE increases decreases decreases increases decreases increases increases decreases TR PD T2 T TE Short TR Long TR decreases increases

32 Timing parameters Spin echo-sequences TR = repetition time, desides the T 1 weighting TE = echo time, desides the T 2 weighting weighting T 1 T 2 PD TR short long long TE short long short Contrast values for IR: PD-w: TE: ms, TR: 2000 ms, TI: 1800 ms T 1 -w: TE: ms, TR: 2000 ms, TI: ms T 2 -w: TE: 70 ms, TR: 2000 ms, TI: ms Flip angle α TE Gradient echo-sequences TR, TE α = flip angle, defines the angle of exitation Longer TR requires bigger α Small (<40 o ) Large (>50 o ) Short (<15ms) PD-w T 1 -w Long (>30ms) T 2 -w -

33 Timing parameters Repetition time TR The amount of time that exists between successive pulse sequences applied to the same slice It is delineated by initiating the first RF pulse of the sequence then repeating the same RF pulse at a time t. Variations in the value of TR have an important effect on the control of image contrast TR is also a major factor in total scan time Echo time TE represents the time in milliseconds between the application of the 90 pulse and the peak of the echo signal in SE and IR pulse sequences 90 o 180 o TE

34 Timing parameters Flip angle α is the angle to which the net magnetization is rotated or tipped relative to the main magnetic field direction via the application of a RF excitation pulse at the Larmor frequencyi The radio frequency power (which is proportional to the square of the amplitude) of the pulse is proportional to α through which the spins are tilted under its influence α=0-90 are used in GE sequences α = 90 and a series of 180 pulses: SE sequence initial 180 pulse followed by a 90 and a 180 pulse: IR sequence Inversion time TI The time period between the 180 inversion pulse and the 90 excitation pulse in an IR pulse sequence The inversion time controls the signal of different tissues and with the change of this parameter also fat and water suppression is attainable.

35 Relaxation times in different 1.5T Tissue Gray matter White matter Spinal fluid fat cartilage muscle blood T 1 (ms) T 2 (ms)

36 TR = ms (1.5T) TE <20 ms (with longer TE one looses T1-contrast on the images) Long TR TE min ms short TR short TE long TR short TE long TR long TE T 1 PD T 2

37 Weighting in different images PDw T 1 w T 2 w T 1 w IR TR/TE=5500/14ms TR/TE=500/10ms TR/TE=5500/101ms TR/TE/TI=2000/14/800ms

38 Advanced techniques

39 Multiplanar reconsturcution multiplanar reconstruction = data set can be reformatted to provide images in different orientations For effective multiplanar reconstruction in brain imaging, images must be obtained with approximately isotropic resolution and a small voxel volume (1x1x1 mm 2, 2x2x2 mm 2 )

40 Volumetric 3D imaging Volumetric imaging is a 3D technique where the signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high SNR The acquisition of isotropix voxels or thin slices with high spatial resolution allows to create multiplanar reconstructions in all planes a compensation for the usually longer scan time The aqcuisition time can be reduced by parallel imaging technique

41 Volumetric 3D imaging New T 2 w variants of 3D sequences (FSE- XETA, T2-SPACE, VISTA) have been introduced that differ from conventional FSE sequences An echo train containing up to 200 echoes obtained at a minimum echo spacing allows very fast acquisition A flip angle modulation (flip angle sweep - FAS) during the FSE readout carries magnetization as long as possible T 2 SPACE

42 3D T 2 Space (Siemens)

43 T1 vibe fs KM 3D

44 Artifacts

45 Artifacts Partial volume Image voxel is containing a mixture of tissue types Loss of contrast between two adjacent tissues Reason: insufficient resolution Help: thinner slices Partial volume: dim brain tissue in the first MRI slice and blurs the edge of the brain in the last slice.

46 Artifacts Cross-talk Appears as a reduced intensity on all but the first slice of a multi-slice set Reason: if the slice gap is too small the edges of the slice may overlap with ist neighbours Help: slice gap minimum 10% Cross talk

47 Artifacts Gradients False gradient strenght leads to geometrical distortion Help: calibrate gradients Unhomogeneity from RF-field Field is not uniform over the whole image Susceptibility/metal artefact Signal dropout, bright spots, spatial distortion Reason: Field inhomogeneity Help: reduce TE or increase resolution Phase wrap-around artefact Produces the image of the tissue at the opposite edge of the scan in the phase-encoding direction (undersampling) Reason: anatomy continues outside the field of view (FOV) Help: use spatial saturation bands just outside the FOV to saturate the signal or larger FOV

48 Artifacts Gibb s artefact/truncation Undersampling in the phase-encode direction Occures at high-contrast boundaries where intensity changes from dark to bright Reason: pixel size is too large to represent accurately the high-contrast boundary Help: phase-encoding matrix should not be less than half the frequency-encode matrix Motion Field is not uniform over the whole image Reason: Movement of the imaged object Ghost Displaced reduplications of image in phase-encoding direction Reason: motion, heart beat, respiration Help: triggering or change the band width

49 Artifacts Zipper Bands through image center Reason: hardware or software problem Help: larger FOV, oversampling, integrety of the RF-shielding in the scan room Magic angle Increase of T 2 time, bright signal in tendons Reason: angle about 55 to the main magnetic field Help: Angle not ~55

50 Clinical MRI applications in radiation treatment planning (RTP)

51 Why use MRI in RTP? Higher resolution on the images One can more clearly identify the tumor in MRI than in CT Leads to more precise dose delivery -> Better response to the radiation therapy treatment

52 tumor CT T1w T1Gd

53 Image fusion CT-MRI 3D CT image in sagittal, axial and coronal plane (Siemens Oncology workstation)

54 3D CT and 3D MRI data set fusion

55 Radiation Therapy Planning When prescribing, recording and reporting radiotherapy treatment, different volumes need to be described [1,2]: gross tumor volume (GTV) clinical target volume (CTV) planning target volume (PTV) organ at risk (OR) [1] ICRU Report 50. Prescribig, recording and reporting photon beam therapy. Bethesda, MD: ICRU, [2] ICRU Report 62. (Supplement to ICRU Report 50). Prescribig, recording and reporting photon beam therapy. Bethesda, MD: ICRU, 1999.

56 Gross tumor volume (GTV) consists of a primary tumour or other tumour mass The size and shape might vary depending on the technique used for evaluation Palpation Mammography ultrasound MRI histological examination of the surgical specimen GTV GTV cannot be drawn as precise borders The zone of uncertainty around GTV depends on the imaging modality, interpretation of imaging or inexperience

57 planning target volume (PTV) In order to achieve a homogenous dose to the CTV, margins must be added to the GTV -> from 5mm up to 2-3 cm uncertainties in patient positioning and alignment of treatment beams during treatment planning and through-out a fractionated course of radiotherapy should be considered PTV should cover the variations (minimal to maximal) caused by brain liquor movements Respiration Bladder/rectal filling swallowing and organ movements PTV

58 Organ at risk (OR) Organs to be spared from the radiation

59 Special techniques

60 What is fmri? Detecting the functional areas in the brain and obtaining at the same time accurate anatomical images of human brain Blood oxygenation level dependent (BOLD) method Stimuli causes a small but detectable change in MR signal intensity in active cortical areas To reveal the active cortical areas statistical and mathematical methods are needed It is important to understand the background of fmri deeper to be able to produce reproducible and accurate results Sequence used is called echo planar imaging (EPI)

61 Background of fmri k-space and image reconstruction The receiver coil integrates the magnetization over the entire volume of the selected slice This signal is a Fourier transform of the magnetization at a single point in a spatial frequency k-space = raw data Important for fmri: how is the raw data collected into the k-space?

62 fmri In standard 2D FT imaging methods only one line in k-space is acquired with each TR interval In contrast, the speed of EPI is based on the possibility to measure the whole k-space applying only one excitation pulse How is this possbile?

63 fmri in standard 2D imaging the frequency encoding gradient is kept constant In EPI, the frequency encoding gradient is rapidly oscillated during the build-up and decay of the echo signals A series of gradient echoes is produced, each one of which is separately phase encoded by application of a phase encoding gradient The contrast in gradient echo EPI images is mainly affected by the spin density and the T 2 * The T 1 -effect is excluded due to the use of only one rf-pulse

64 Advanced Segmentation based on fmri for Radiation Therapy Brain tumors and surgery may shift the functional areas of the brain. With functional magnetic resonance imaging (fmri) it is possible to detect functional areas, including anatomical information of an individual patient. This is crucial for e.g. localization of Broca s and Wernicke s areas it is also important for radiation therapy when planning to save these areas

65 Advanced Segmentation based on fmri for Radiation Therapy 3D fmri can be fused with 3D planning CTs to get valuable information about the speech center localization and shifting during radiation therapy This process will improve the planning process and the definition of the radiation target volume

66 (A) CT (B) fused CT and fmri (C) Areas activated under the speech task are drawn on the maps.

67 Radiation therapy plan, where speech locations (Broca) is being drawn with green and surgical cavity coloured red. Fused grayscale CT and fmri images (A-C) displaying the target volumes (Oncologist, Siemens).

68 Diffusion Tensor Imaging (DTI)

69 DWI Diffusion MRI is a method that produces images of biological tissue weighted with the local microstructural characteristics of water diffusion The field of diffusion MRI has two applications Diffusion Weighted MRI Diffusion Tensor MRI DWI DTI

70 Background of DWI The diffusion tensor elements (D xx, D xy, D yz, ) are patientorientation-dependent. To eliminate this dependency, the diffusion tensor matrix can be diagonalized to the following form: D = D D D 3 λ 2 λ 3 D 2 D 3 D 1 λ1 This is equivalent to using a new coordinate system that is aligned along the three axes of the diffusion ellipsoid at each spatial encoding The elements D 1, D 2 and D 3 are known as characteristic values or eigenvalues (λ) of the matrix

71 Diffusion imaging The sum of the three eigenvalues is the trace of the diffusion tensor In trace images the contrast is generated by the direction of the diffusion tensor This parametric images contains the average of the three eigenvalues (independent of the frame of reference) For example, if one eigenvalue is considerably larger than the two others (such as in the case of white-matter fiber tracts in the brain), the largest eigenvalue is referred to as the principal diffusion coefficient and its eigenvector (e.g. each eigenvector D i (i=1, 2, 3) corresponds to a characterisrtic vector, eigenvector) is aligned along the principal diffusion direction Ones the eigenvalues are known, a number of diffusion parameters can be produced

72 From DWI to DTI The measured rate of diffusion will differ depending on the direction from which an observer is looking In DTI, each voxel has one or more pairs of parameters: a rate of diffusion a preferred direction of diffusion (described in terms of three dimensional space) The properties of each voxel of a single DTI image is usually calculated by vector or tensor matrix from several different diffusion weighted acquisitions, each obtained with a different orientation of the diffusion sensitizing gradients DTI it extremely sensitive to subtle pathology in the brain neural tracts can be followed through the brain tractography

73 Example DTI implemented in radiation therapy: White matter tracts (WMT) known to be a pathway for GBM dissemination DTI can show disruption of water diffusion in white matter tracts as a surrogate for tumor spread DTI may permit more accurate target localisation for radiotherapy

74 T1 MRI T1 MRI fused with DTI T2 MRI Patient X Tracts in 3-D Neuro 3D, Siemens

75 Fused1.5 T DTI MRI and 2 mm CT Patien t Target volume Volu me (cm 3 ) % reduction Patient 3 3 cm PTV 1 Clinical DTI- PTV *DTI-PTV *CTV T2 MRI + 5 mm 1 cm PTV 2 Clinical DTI- PTV GTV T1 MRI 3 Clinical white matter tracts DTI- PTV

76 Dosis distribution GTV PTV tracts

77

78 Thank you for your attention.

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