1. Proton beam range verification using off-site PET by imaging novel proton-activated markers
J Cho, G Ibbott, M Kerr, R Amos, and O Mawlawi
The University of Texas MD Anderson Cancer Center, Houston, TX
M21-4, IEEE-MIC 2013 meeting, Seoul, Korea
Motivations
The conventional proton range verification using PET takes advantage of endogenous tissue activation in combination with Monte Carlo simulation. However, this approach has the following limitations:
Weak tissue activation at the end of the proton beam
Perfusion driven activity washout
Short decay half-life (need of costly in-room PET)
Monte Carlo related uncertainties in
Elemental tissue composition conversion
Nuclear cross sections
Biological washout model
Therefore, we developed a novel proton range verification method that is not subject to the above limitations. By taking advantage of patient-implantable fiducial markers that are strongly activated by low energy protons and which decay with relatively long half-lives, a proton range verification can be realized using commonly available off-site PET scanners.
Previously we showed that when 68Zn and Cu markers are placed along the distal end of the proton beam range, they result in higher PET signals than surrounding material such as plastic water and balsa wood following proton treatment (Cho et al PMB 58 (2013) ).
In this work, we performed two pseudo clinical studies to verify the proton range in lung and soft-tissue equivalent materials. The PET activation of different volumes of 68Zn and Cu markers embedded in balsa wood and beef phantoms following proton irradiation were compared to isodose curves (or PDD) to predict the proton range.
Methods & Materials
Results
(a) (b)
1 volume (25 mm3) of 68Zn markers and 3 volumes
(10, 25, 50 mm3) of Cu markers were embedded at each
location along 4 different depths.
(c)
(d)
(a)
Fig. 6: PET/CT fusion images acquired for 30 min from a balsa wood phantom after a 60 min post-irradiation delay. (a) and (b) are coronal views showing strong PET signals from markers. (c) Markers at depth 4 and depth 5 show signal and no signal, respectively. Proton range estimation within ±2 mm is achievable if maker at depth 5 is separated by 4 mm from depth 4. (d) Isodose curves overlaid on CT coronal plane.
▪ 68Zn and Cu markers located at higher dose than 50% PDD (depth 4) show PET signals. Markers located at lower PDD (depth 5) do not show PET signals. This information can be used to estimate PDD (or proton range) from signals of markers located at different depths.
▪ Only markers of volume > 25 mm3 show signals.
(b)
Fig. 4: (a) Balsa wood (as lung substitute) phantom with embedded 68Zn and Cu markers at 4 distal fall-off depths and irradiated by a proton beam. (b) Locations of embedded markers relative to PDD (percentage depth dose). Natural Cu was used due to its relatively high 63Cu content (69%).
Background
→ 60 min post-irradiation delay and 30 min PET scan
(a)
Fig. 1: Proton range uncertainty can result in overdosage in critical organs or underdosage in tumor. It is crucial to verify the proton range accurately.
(b)
(a)
(c)
Fig. 2: 68Zn and 63Cu have large cross sections at low proton energies and decay with relatively long half-lives. As a result, they are activated strongly at the proton distal fall-off region where proton energy is low. Endogenous tissue elements (12C and 16O) are shown for comparison.
(b)
Fig. 5: (a) Beef phantom (as soft-tissue substitute) cut diagonally is embedded with 68Zn and Cu markers and is irradiated by a 160 MeV proton beam. Each coronal plane contains a different marker volume. (b) Locations of embedded markers relative to PDD.
Fig. 7: Beef phantom experiment. In each subpart, the top image shows the PET/CT fusion images acquired for 30 min and the bottom image shows the isodose curves overlaid on the CT of the same slice. Marker locations are shown for correlation. (a) 1st row - four 25 mm3 Cu markers. (b) 3rd row - four 25 mm3 68Zn markers. (c) 5th row - four 50 mm3 Cu markers.
▪ 68Zn markers located at higher dose than 50% PDD show PET signals, however, Cu markers located at higher dose than 95% PDD show PET signals which is different from Fig 6’s results (which was 50%PDD). It is because the post-irradiation delay is longer (120 min) and radioisotopes created (from activated Cu) at a deeper PDD depth decay with a shorter half-life.
▪ Only markers of volume > 25 mm3 show signals.
Modified from Parodi et al, NIH public access 2007
Proton
range
→ 120 min post-irradiation delay and 30 min PET scan
All irradiated phantom were then moved to an offsite D-690 PET/CT scanner (GE Healthcare, Waukesha, WI) and imaged. A CT scan was first acquired followed by a PET scan in List mode for 30 min. All PET data were then reconstructed using OSEM iterative techniques using standard manufacturer software.
(a) (b)
Conclusions
Relatively high PET signals were obtained from 68Zn and Cu markers of volume > 25 mm3 compared to background for balsa and beef phantoms at the proton distal dose fall-off region when scanned for 30 min with post-irradiation delays of 60 min and 120 min, respectively. This indicates the possibility of using those markers as patient implantable fiducial markers in both the lung and soft-tissue for proton range verification using off-site PET scanners. While 68Zn markers show signal as low as 50% PDD irrespective of post-irradiation delay time, Cu markers show signal as low as 50% PDD for 60 min delay but only to PDD 95% for 120 min delay. This delay factor should be considered to estimate the PDD (or proton range) from PET signals generated from 68Zn and Cu markers. Proton range can be defined at any PDD such as 50% PDD or 95% PDD.
Fig. 3: Hypothetical images of proton activated fiducial markers made of 68Zn or 63Cu implanted in a patient prior to proton therapy. (a) One marker is implanted near the proton distal fall-off and one just outside the proton range. (b) The marker implanted near the distal fall-off is activated (red) and the other marker outside the proton range is not activated (green). In this regard, the proton range can be approximated to be somewhere between the two markers (Yellow line).