Functional and Molecular Imaging for Radiation Therapy Guidance

Transcription

1 Functonal and Molecular Imagng for Radaton Therapy Gudance Imagng 3D modelng Treatment plannng Pt setup and treatment delvery L Xng, T L, Y Yang, E. Schrebmann, B Thorndyke, D. Spelman 3D/4D CBCT Department of Radaton Oncology Stanford Unversty School of Medcne 4D magng Bologcal magng 4D modelng 4D plannng Gated tx plannng Adaptve therapy (magng, plannng, delvery) Day 0 Day 14 Day 24 Targetng n current radaton oncology /CT Intra-fracton organ movement, n partcularly, respratory moton Where s the tumor? Inter-fracton organ movement Target volume defnton & localzaton Is tumor respondng to therapy? Anatomc Imagng Tssue Characterzaton and Classfcaton Molecular Imagng 19 July July 2000 Pre-treatment stagng & plannng Treatment plan for prostate patent wth nodal rsk>15% 50% 90% 100% Stagng Restagng 21 September August 2000 Anteror Feld Lateral Feld Axal Feld Prognoss Treatment plan for prostate patent wth nodal rsk <15% Montorng Treatment A. Quon

2 Shortcomngs of Current Radaton Therapy Where s the tumor? Where s the boundary of the tumor? Stagng and treatment decson-makng are based largely on anatomcal magng. Tumor volume defned on CT/MRI may often be too small or too large. The whole Rx course takes 5-6 weeks and there s no effectve tools to dstngush responders from un-responders. Detecton of recurrence s problematc. Spatal bology dstrbuton s not consdered. What s the bology dstrbuton? Imagng 3D modelng Treatment plannng Pt setup and treatment delvery IMRT provdes an unprecedented means to produce customzed 3D-dose dstrbutons wth sub-cm resoluton. Integraton of radologcal magng technques allows better patent postonng and dose delvery. 4D magng Bologcal magng 4D modelng 4D BCRT plannng 3D/4D CBCT Adaptve therapy (magng, plannng, delvery) Functonal/metabolc magng modaltes are avalable for nonnvasvely provdng crtcal needed metabolc and physologcal data. Day 0 Day 14 Day 24 Molecular magng technques are emergng. The Current Imagng Toolbox Integraton of bologcal and functonal Image. -- Bologcally Conformal Radaton Therapy (BCRT) Method CT MRI MRSI SPECT HFUS Optcs Mnmum Detectable Sze (φ)( 1~2 mm 1~2 mm 7 mm (~3mm at 3T) 4~6 mm 3~5 mm <1 mm 0.02 mm Mnmum Detected Cells (n) 400, ,000 1,000, , , , to truly ndvdualze radaton therapy

3 day1 day4 day8 Lucferase--Transcrptonal Reporter Bench-top Small Anmal Imagng System: Macroscope ATP ADP + P hν Lucferase Mg Lucfern Oxylucfern Day11 after noculaton P Maxm, S Gambhr, C Contag, and L Xng, Molecular Imagng. Exctaton Fluorescence Project n Cellular & Molecular Imagng Stanford Unversty Medcal Center (C. Contag) Genome Emsson Emsson Promoter O 2 Substrate & energy Lucferase Bolumnescence Genome Emsson Emsson Clncally avalable molecular/functonal magng tools Endorectal Col-Based 3T MR Spectroscopc Imagng for Radotherapy MR Spectroscopc Imagng (MRSI) Functonal MRI, DWI/DTI, SPECT 3T Endorectal Probe MRSI: montor the molecular propertes of a tumor ER Col----hgh SNR MRI/MRSI ER Col----severely dstorts the prostate and /CT Topc Characterzaton of Tssue Stagng Restagng/Prognoss Montorng Treatment Emergng Applcatons Example Soltary Pulmonary Nodules Lung Cancer Lymphoma/Breast Cancer GIST, Breast CA, Lymphoma XRT plannng Approprate management decsons starts wth accurate stagng changes overall management n more than 30% of cases Gambhr, et al 2001 Dzendorf et al, JNM 44, 24-29, 2003

4 /CT for Radaton Therapy Commonly used postron emtters delneate target volume assess therapeutc response dstngush recurrent tumor and radaton necross Isotope 11 C Half-lfe lfe (mn.) 20 Producton method Cyclotron Max. range n water (mm) 1.1 Applcaton Producton 11 C-CholneCholne 11 B(p,n) 11 C 13 N 10 Cyclotron N ammona 13 C(p,n) N Pre-treatment /CT/MRI /CT/MRI-based tumor delneaton Plannng & treatment Post-treatment /CT/MRI 15 O 18 F 68 Ga hr Cyclotron Cyclotron Generator O water 14 N(d,n) O FDG, FLT 19 F(p,pn) 18 F 18 O(p,n) 18 F Regstraton & analyss 82 Rb 1.3 Generator 1.7 FLT, 11 C-cholne, 18 F-cholne, Acetate, F-Dopa, Cu-ATSM, F-MISO, F-EF5 Receptors and peptde-based tracers. Prolferaton magng Buck et al., J Nucl Med, 2003 Post-treatment Functonal Image-Guded IMRT Pre-treatment Post-treatment Relable magng tools. Integraton---network transfer of functonal mage fles, fle format converson, mage fuson/deformable mage regstraton. Image fuson. Inverse treatment plannng. Qualty assurance. Clncal study of the effcacy.

5 Example: 4D Patent setup CTAC (best at expraton) RPM system GE gated Recon selected gates 4D plannng A Lver Cancer patent GE 4D 1 cm Conventonal 3D Stanford new 4D technque If bn sze = t, then n each respratory cycle: Bn 1 accumulates events from [0, t] Bn 2 accumulates events from [ t, 2 t] Bn 3 accumulates events from [2 t, 3 t]... Bn N accumulates events from [(N-1) t, N t] 3D --- the leson n the ungated mage s elongated, and mslocalzed superorly by ~1 cm. GET locaton s rght but sgnal s week. RS 4D locaton and sgnal are great. 3D gve wrong locaton and wrong volume R N C CNR Ungated Gated at Insp wth 1.25 sec Retro. Stacked at Insp cranocaudal locaton (mm) RS 4D magng technque coronal sagttal Functonal Image-Guded IMRT Relable magng tools. Image fuson. Inverse treatment plannng. Stanford 4D mage at end-nspraton. The leson has clearly emerged from the background actvty at the end-nspraton locaton. Qualty assurance. (B. Thorndyke, E. Schrebmann, A. Koogn, and L. Xng, Med Phys, 2006). Image Regstraton Hardware Fuson CT mages Automated regstraton based on control volume(s). CT scan Raw CT data 20 mn tmesavng Scatter and attenuaton correcton scan Raw data Schrebmann and Xng, Med. Phys., ~ 8 mn per coach poston mages

6 Head and neck CT,, and IMRT treatment plan CT CT Deformable mage regstraton 4D Image Regstraton E. Schrebmann and L Xng, IJROBP, 2006

7 Functonal Image-Guded IMRT Bologcal mage based nverse treatment plannng Relable magng tools. 3 SD 5 SD 7 SD Image fuson. Inverse treatment plannng. Qualty assurance. /MRI/MRSI Inverse plannng Post-scan data processng Quantfy metabolsm Prescrpton Beam orentaton/profle optmzaton Fne-tune regonal doses Plan revew MLC leaf sequencng IMRT Plan Incorporatng MRSI data Bologcally Conformal Radaton Therapy Bologcal magng Spatal dstrbuton of bologcal parameters SD=3 95% 40% Target 3 (SD=3) Spatally nonunform conformal dose dstrbuton SD=5 50% Target 2 (SD=5) SD=7 20% 40% Tssue Target 1 (SD=7) Dose (Gy) L. Xng et al, PMB 47, , Prescrpton for molecular/functonal mage guded IMRT Functonal Image-Guded IMRT TCP = exp[ ρ0 v exp( α D + γ T )] Relable magng tools. α r 1 1 α rρ0r D = Dr ( γ r γ ) T ln α α α αρ0 Image fuson. Inverse treatment plannng. Qualty assurance. Yang Y and Xng L, Med. Phys

8 Qualty Assurance Relatonshp between the Cho/NAA ratos of the calbraton solutons obtaned at 9.4 T versus the calbraton-soluton-flled vals nsde the phantom obtaned at 1.5 T usng a 2D PRESS sequence. S. Hunjan, D. Km, A. Adalstensson, D. Spelman, L. Xng, IJROBP 57, , 2003 S. Hunjan, D. Km, A. Adalstensson, D. Spelman, L. Xng, IJROBP 57, , D Image Enhancement - Phantom Valdaton Functonal Image-Guded IMRT CNR R N C Ungated Gated wth 0.4 sec Gated wth 1.0 sec Retro. Stacked superonferor locaton (mm) Moton drecton Moton drecton 3D 4D (after postacquston data processng usng our new algorthm) Intensty profles along the moton drecton B. Thorndyke, E. Schrebmann, A. Koong, L Xng, Med. Phys (B. Thorndyke, E. Schrebmann, A. Koogn, and L. Xng, IJROBP). Relable magng tools. Image fuson. Inverse treatment plannng. Qualty assurance. A lot of research! Summary Functonal/molecular magng s emergng. day1 day4 day8 Next Generaton Radaton Therapy Integraton of functonal & molecular magng Bologcally Conformal IMRT ----to truly ndvdualze Rx Day11 after noculaton Relable magng tool, regstraton, nverse plannng, QA, research. P Maxm, S Gambhr, C Contag, and L Xng, Molecular Imagng., 2004

9 ACKNOWLEDGEMENTS Former postdocs- S. Hunjan, J. Lan, Clncal faculty A. Koong, K. Goodman, Q. Le, S. Hancock, A. Quon Physcst G. Luxton, T. Pawlck, P. Maxm,. Fundng agency NIH (1R01 CA98523 & 1R01CA104205) DOD (PC )