Use of molecular and functional imaging for treatment planning The Good, The Bad and The Ugly

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1 Use of molecular and functional imaging for treatment planning The Good, The Bad and The Ugly Robert Jeraj, PhD Associate Professor of Medical Physics, Human Oncology, Radiology and Biomedical Engineering University of Wisconsin Carbone Cancer Center, Madison, WI Molecular and functional imaging Molecular Imaging: Visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems It can probe molecular abnormalities that are the basis of disease rather than image the end effects Functional Imaging: Visualization, characterization and measurement of organ function in humans and other living systems It can probe functional status of an organ, which is direct consequence of disease or treatment See in vivo what we can see in vitro Paradigm shift in imaging Microscopy 1 mm cm PET/CT imaging From QUALITATIVE DIAGNOSTIC IMAGING (Diagnosis and Staging) To QUANTITATIVE THERAPEUTIC IMAGING (Target definition, Treatment assessment) Courtesy of A. van der Kogel, Nijmegen, NL Proliferation Hypoxia Limited experience with imaging in treatment context, compared to diagnostic (except CT)! Dangerous to use diagnostic quality imaging in a therapeutic context (Qualitative Quantitative) 1

2 PET imaging uncertainties Imaging in oncology Technical factors Relative calibration between PET scanner and dose calibrator (10%) Residual activity in syringe (%) Incorrect synchronization of clocks (10%) Injection vs calibration time (10%) Quality of administration (0%) Physical factors Scan acquisition parameters (1%) Image reconstruction parameters (30%) Use of contrast agents (1%) Analytical factors Region of interest (ROI) definition (0%) Image processing (2%) Biological factors Patient positioning (1%) Patient breathing (30%) Uptake period (1%) Blood glucose levels (1%) Jeraj 2010 Boellaard et al 2009, J Nucl Med 0: 11S ANATOMICAL MOLECULAR BEFORE DURING AFTER THERAPY DIAGNOSIS and STAGING TARGET DEFINITION IGRT... EARLY LATE TREATMENT ASSESSMENT Imaging in oncology Target definition ANATOMICAL MOLECULAR IGRT ~1980 Discrete volume ~1990 Conformal therapy IMRT BEFORE DURING AFTER THERAPY DIAGNOSIS and STAGING... TARGET DEFINITION EARLY LATE TREATMENT ASSESSMENT 2

3 2D OSEM 3D ITER Current state of affairs What is the real tumor extent? Hong and Harari, 200 Daisne et al 2004, Radiology 233, 93. Different modalities different answer Same modality different answers 26, 2 iterations 26, 2 iterations 128, 2 iterations 128, 2 iterations 128,4 iterations 3 mm filter width 6 mm filter width 3mm filter width 6 mm filter width 6 mm filter width SUV 10 26, 2 iterations 26, 2 iterations 128, 2 iterations 128, 2 iterations 128,4 iterations 3 mm filter width 6 mm filter width 3mm filter width 6 mm filter width 6 mm filter width 0 Daisne et al 2004, Radiology 233, 93. 3

4 Avg. Margin Axial Plane (mm) Max. Margin Axial Plane (mm) Imaging uncertainties extra margins And here comes DOSE PAINTING Patients Patients Margin plane Mean ± SD (mm) Maximum (mm) Avg. Max ± SD (mm) Maximum (mm) Axial 1.0 ± ± Coronal 0. ± ± Sagittal 0. ± ± Ling et al 2000, Int J Rad Oncol Biol Phys 47: 1 Spatial distribution of tumor phenotypes Spatial distribution of tumor phenotypes (metabolism) FLT PET/CT (proliferation) Cu-ATSM PET/CT (hypoxia) (metabolism) FLT PET/CT (proliferation) Cu-ATSM PET/CT (hypoxia) 4

5 Other How to combine this information? Proliferation [ 18 F]FLT Uniform dose Non-uniform dose Proliferative and hypoxic Hypoxia [ 64 Cu]Cu-ATSM? Proliferative Hypoxic Anatomical imaging Population-based Uniform dose IMRT Molecular imaging Patient-specific Non-uniform dose IMRT Symposium Yue Cao: MRI for Radiation Treatment Planning Dimitris Visvikis: The Good, the Bad and the Ugly About Using PET for Treatment Planning Vincent Gregoire: This House Believes That the Use of Functional Imaging for Treatment Planning of Head and Neck Tumors Need to be Carefully Considered