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<p>The thesis has two parts. The first project relates to real time dosimetry in Gynecological
(GYN) High Dose Rate (HDR) Brachytherapy Treatments and the second part investigates
a new workflow for Image Guided Brachytherapy (IGBT) for centers that do not have
access to MRI with applicator in-situ.</p><p>Project 1: Real-time Dosimetry in HDR
Brachytherapy using the Duke designed NanoFOD dosimeter: Limits of Error Detection
in Clinical Applications</p><p>Purpose: Previously, an optical fiber radiation detector
system was shown to be capable of identifying potential high dose rate (HDR) brachytherapy
delivery errors in real time. The purpose of this work is to determine this detector’s
limits of error detection in vaginal cylinder and tandem and ovoid-type HDR gynecological
brachytherapy treatments.</p><p>Method and Materials: The system consists of a scintillating
nanoparticle-terminated fiber-optic dosimeter (NanoFOD) and a LabView platform (Versions
2015 and 2017; National Instruments Corporation, Austin, TX) which displays the real-time
voltages measured by the NanoFOD during HDR treatment delivery. The platform allows
for the measured voltage to be overlaid on the expected detector signal. To test the
limitation of error detectability in vaginal cylinder brachytherapy, the NanoFOD was
taped 1.5-cm from the tip of a 3-cm diameter Varian manufactured stump cylinder. This
setup was </p><p>imaged using CT to localize the NanoFOD, and a plan was generated
based on one of the institutional 3-cm stump cylinder templates with 9 dwell positions.
For each dwell position, the expected voltage and doses were calculated using the
dose distribution exported from the treatment planning system (TPS), a previously
obtained distance-based calibration curve for the NanoFOD and TG-229 along and away
table. The voltage values were imported to the LabView for real time monitoring.
With a known location of the NanoFOD tip, the expected doses from the NanoFOD at each
dwell position were calculated for all applicators for: 1) the clinical plan; 2) wrong
source guide tube (SGT); 3) wrong cylinder; 4) wrong treatment template; 5) wrong
step size, as well as 6) incorrect positioning of the cylinder insert. Measurements
of voltage from each delivered plan were converted to dose per dwell and compared
to the expected dose values.</p><p>In addition to experiments, a simulation-based
limit of error detection with cylinder was studied and the results obtained from simulation
were compared to experimental results. Simulation was done by modifying the applicator
parameters and the incorrect plans were generated for 1) wrong SGT lengths 5-mm to
70-mm longer than correct length with a 5-mm interval; 2) wrong cylinder; 3) wrong
treatment template; 4) wrong step size, as well as 5) incorrect positioning of the
cylinder insert. Doses per dwell were also calculated and compared to the doses from
correct plan. </p><p>Furthermore, simulations-only for T&O plans were also performed.
Two representative clinical T&O-based plans with extra needles were used to establish
the simulation-based limits of error detectability of the NanoFOD system. With a known
location of the NanoFOD tip, the expected doses from the NanoFOD at each dwell position
were calculated for all applicators for: 1) the clinical plan; 2) wrong treatment
lengths (TL); 3) wrong connection to afterloader; 4) wrong digitization direction;
and 5) wrong step size. </p><p>From previous work, it has been determined that the
overall uncertainty in dose of this system in HDR brachytherapy is 20%. The percent
difference (PD) between expected and measured doses and, between the simulated doses
from correct and incorrect plans was calculated and compared to 20% to determine if
a certain potential error can be detected with the NanoFOD system.</p><p>Results:
For the cylinder experiments, when the correct treatment was delivered, the median
PD over 9 dwells between measured and expected dose from each dwell was 11%. When
the wrong SGT, wrong cylinder size, or wrong clinical template was used, the system
detected PD values of -91.6%, -71.4% and -29.6% at the first dwell. With wrong step,
the system showed large discrepancies starting at the third dwell position (58.6%).
When incorrect cylinder insert length was 0.5cm, 1.0cm and 1.5cm, the significant
PD values captured were -29.4%, -28.1% and -22.5% at 3rd, 2nd and 1st dwell, respectively.
</p><p>In TPS simulations for the cylinder applicator, PD from wrong SGT, wrong cylinder
size and wrong template and were -93.6%, -90.8% and -57.8% at first dwell. For wrong
step size, the simulation predicted the PD to be greater than 20% (47.2%) starting
at first dwell. For all incorrect insert length, simulation predicted greater than
20% PD (-38.6%, -34.9%, -38.6%) at first dwell. For incorrect SGT lengths range from
5mm to 70mm, simulation-based PD was from -28.0% to -82.3% at the first dwell, indicating
the NanoFOD caught this error when the SGT was only 5-mm longer.</p><p>In TPS simulations
with two T&O-based plans, with incorrect treatment length (TL, 5mm-70mm), the PD ranges
for the two patients were 26.4%-26.8%, 20.4%-30.9%, and 30.9%-57% in 10mm TL tandem,
5mm TL ovoid and 10mm TL needle at first dwell. PD values were -44.1% to -36.4%, -75.3%
to 96.4%, and -39.6% to 298.1% respectively at the first dwell when connections between
tandem and left ovoid, left needle and left ovoid, left needle and tandem were swapped.
When the two needles were switched, PD values were 43.1% and 63.6% at the 1st and
3rd dwell for patient A and patient B. Switching connection between the two ovoids
did not produce significant PD for patient A because the two ovoids were identically
loaded. For patient B, the PD was 87.5% when ovoids were swapped. Incorrect direction
of digitization made the signal too low to be detected, an indication that treatment
should be stopped. With wrong step size in tandem, ovoid and needle, simulation-based
PD range in dose for two patients were 25.8%-34.9%, 34.3%-37.4%, and 20.7%-81.5%,
respectively at 3rd, 2nd and 1st dwell for both patients.</p><p>Conclusion: </p><p>Using
the 20% error detection threshold, the NanoFOD system was able to detect errors in
real time cylinder tests when the wrong cylinder size, wrong SGT and wrong template
were used, all at the first dwell position. For subtle errors such as small incorrect
catheter insertions, the real-time system can detect errors starting with the second
or third dwell position. The Labview interface is a good tool to use for real time
tracking of the delivery. </p><p>TPS simulation predicted comparable discrepancies
to PD obtained from experimental measurements when wrong cylinder size and wrong source
guide tube was used. The disagreement between simulation-based PD and experiment-based
PD is due to uncertainty in positioning during the experiment, as the nanoFOD in current
form does not have a radio opaque marker to help with easy identification. TPS simulation
was thus used for more complex applicators, knowing that simulations and experiments
match.</p><p>With the 20% PD as an indication of wrong treatment in T&O-based HDR
cases, the NanoFOD can capture all simulated gross errors within the first few dwells
into the treatment, indicating it is capable of real-time verification of T&O HDR
brachytherapy. Although the two T&O plans were different, the NanoFOD was able to
capture the errors at similar dwell positions regardless of the difference in planning.
Overall, the NanoFOD can catch, in real time, potential gross errors in clinical HDR.</p><p>Project
2: Investigation of Contour-based Deformable Image Registration (cbDIR) of pre-brachytherapy
MRI (pbMRI) for target definition in HDR cervical cancer treatments</p><p>Purpose:
While MRI-guided brachytherapy has been considered the gold standard for IGBT treatment
for cervical cancer, practical factors such as cost, MRI access and clinical flow
efficiency have limited the use of MRI for brachytherapy treatments. However, a pre-brachytherapy
MRI (pbMRI) is usually taken before the brachytherapy to assess the tumor regression
after external beam treatments. The purpose of this project is to investigate the
role of contour-based deformable image registration of the pbMRI in target definition
for high dose rate (HDR) cervical cancer treatments.</p><p>Method and Materials: Thirty-five
patients with locally advanced cervical cancer treated at Duke University with Tandem
and Ovoids (T&O) applicators were studied. A pbMRI was acquired for all patients.
Each patient also had MRI and CT taken with applicator in situ at the time of the
first fraction. The uterus structure contoured on pbMRI was deformed using contour-based
(cb) and hybrid contour-based (hcb) DIR to the same structure contoured on the CT
of first HDR fraction (MIM Software Inc., v 6.7.3 and v 6.8.11). The deformation matrix
was used to deform the dHRCTV, which was then compared with the ground truth HRCTV
(gtHRCTV) obtained on the MRI of 1st HDR fraction. Dice Similarity Coefficients (DSC)
and Hausdorff Distance (med_HD, max_HD) were used to evaluate the overlap and mismatch
at boundaries between the deformed HRCTV and gtHRCTV using both DIR methods. The process
of generating dHRCTV requires user’s manual input. Therefore, inter- and intra-user
variability using cbDIR, as well as the difference in the two DIR methods were investigated.
</p><p>Results: The pbMRI scan was acquired on average 5.9+/-3.8 days before first
HDR fraction. Median DSC for uterus was 0.9 (IQR 0.88-0.93) and 0.93 (IQR 0.92-0.94),
and for HRCTV was 0.64 (IQR 0.52-0.71) and 0.68 (IQR 0.59-0.72) for cbDIR and hcbDIR,
respectively. The median med_HD for uterus was 0.09cm (IQR 0.08-0.1cm) and 0.08cm
(IQR 0.06-0.09cm). The median max_HD for HRCTV was 1.37cm (IQR 1.1-2.3cm) and 1.39cm
(IQR 1.1-1.6cm) with cbDIR and hcbDIR respectively. Limited inter-user, intra-user,
and DSC variability between DIR versions were found (p=0.53, p=0.77, p=0.18, respectively).
</p><p>Conclusion: Contour-based DIR based on uterus/cervix structure is proven to
be relatively user independent, improves when hybrid contoured based DIR algorithms
are used, and is expected to serve as a good starting point for HRCTV definition for
HDR planning in the absence of MRI with applicators in-situ.</p>
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