Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Medical Physics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Geoffrey Ibbott

Committee Member

Osama Mawlawi

Committee Member

Michael Gillin

Committee Member

Carlos Gonzalez-Lepera

Committee Member

Francesco Stingo

Committee Member

Harald Paganetti


Positron emission tomography (PET), a tool commonly used for cancer staging and response monitoring, has recently been used for proton therapy verification. By imaging tissue activation following proton treatment, attempts have been made to verify proton dose and range. In this dissertation, two novel approaches were developed and tested for the purpose of help improve the proton dose and range estimation as well as verification.

Although there are still some challenges, attempts for proton dose verification using PET has been made by comparing Monte Carlo dose and PET simulations with treatment planned dose and measured PET. In this approach, generic tissue composition information is used which can cause large uncertainties in Monte Carlo PET simulation. To improve these uncertainties, we developed a method in the first part of the research to obtain tissue elemental composition using PET after proton therapy. Proton activation of tissue creates progeny radioisotopes according to constituting tissue elements’ cross sections and proton energies. The time-activity-curves from activated tissues can be separated into constituting progeny radioisotopes using a least squares method and then to constituting elemental compositions using Monte Carlo simulated proton energy and cross-section information. We tested this approach using a phantom consisting of sections composed of different combinations of 12C and 16O irradiated using a mono-energetic and a SOBP proton beam. In addition, two patient studies were also evaluated using the same technique immediately after proton treatments. The 12C and 16O compositions were estimated within 3.6% accuracy in the phantom studies and within 15.2% for patient studies. The obtained tissue elemental composition can be used to improve proton dose verification using PET.

In the second part of this dissertation, we developed a new approach to verify proton range. Conventional proton range verification is performed by correlating the distal end of measured PET signals to the proton range. However, this approach is affected by minimal tissue activation near the end of the proton range, perfusion-driven activity washout, and short half-lives of progeny radioisotopes. This also requires an in-beam, in-room, or on-site PET scanner which can be financially and technically challenging for many proton centers. Our new approach overcomes all of these limitations by using proton activated markers. When implanted near the proton distal end, those markers are strongly activated while tissues are minimally activated. For this work we tested 18O enriched water, Cu and 68Zn enriched markers that were embedded in tissue-equivalent materials and imaged using an off-site PET scanner following proton activation. The marker materials provided significantly stronger PET signals near the distal end which can be used to verify proton range. In addition, optimal volumes of those markers were also investigated when imbedded in tissue-equivalent materials while using clinical treatment and imaging scenarios. Our results suggest that marker volumes ranging between 5 and 50 mm3 are required to provide adequate PET signals. The proposed approach can potentially replace conventional fiducial markers with the added benefit of proton range verification.

Two proposed methods performed in this research can be used potentially improve both proton dose verification using PET and proton range verification using an off-site PET.


positron emission tomography (PET), proton therapy verification, proton range verification, elemental composition, radioactive decay, implantable marker, proton activation, 18O, 63Cu, 68Zn



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