Changes in Eye Tracking Features Across Periods of Overpressure Exposure.

INTRODUCTION: Repetitive exposure to blast overpressure waves can be a part of routine military and law enforcement training. However, our understanding of the effects of that repetitive exposure on human neurophysiology remains limited. To link an individual's cumulative exposure with their neurophysiological effects, overpressure dosimetry needs to be concurrently collected with relevant physiological signals. Eye tracking has shown promise for providing insight into neurophysiological change because of neural injury, but video-based technology limits usage to a laboratory or clinic. In the present work, we show capability for using electrooculography-based eye tracking to enable physiological assessment in the field during activities involved repetitive blast exposures. MATERIALS AND METHODS: Overpressure dosimetry was accomplished by using a body-worn measurement system that captures continuous sound pressure levels as well as pressure waveforms of blast event in the range of 135-185 dB peak (0.1-36 kPa). Electrooculography eye tracking was performed using a commercial Shimmer Sensing system, which captured horizontal eye movements of both the left and right eyes, as well as vertical eye movements of the right eye, from which blinks can also be extracted. Data were collected during breaching activities that included repetitive use of explosives. Participants in the study were U.S. Army Special Operators and Federal Bureau of Investigations special agents. Approval for research was received by the Massachucetts Institute of Technology Committee on the Use of Humans as Experimental Subjects, the Air Force Human Research Protections Office, and the Federal Bureau of Investigations Institutional Review Board. RESULTS: The energy from overpressure events was accumulated and summarized into an 8-hour equivalent of sound pressure level (i.e., LZeq8hr). The total exposure in a single day, i.e., the LZeq8hr, ranged from 110 to 160 dB. Oculomotor features, such as blink and saccade rate, as well as variance in blink waveforms, show changes across the period of overpressure exposure. However, the features that showed significant change across the population were not necessarily the ones that showed significant correlation with the levels of overpressure exposure. A regression model built to predict overpressure levels from oculomotor features alone showed a significant association (R = 0.51, P < .01). Investigation of the model indicates that changes in the saccade rate and blink waveforms are driving the relationship. CONCLUSIONS: This study successfully demonstrated that eye tracking can be performed during training activities, such as explosive breaching, and that the modality may provide insight into neurophysiological change across periods of overpressure exposure. The results presented herein show that electrooculography-based eye tracking may be a useful method of assessing individualized physiological effects of overpressure exposure in the field. Future work is focused on time-dependent modeling to assess continuous changes in eye movements as this will enable building dose-response curves.

Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients.

PURPOSE: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. METHODS AND MATERIALS: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. RESULTS: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). CONCLUSIONS: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.

Spatial mapping of functional pelvic bone marrow using FLT PET.

The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukey's multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging.

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PURPOSE: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. METHODS AND MATERIALS: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. RESULTS: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. CONCLUSION: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [(18)F]FLT PET imaging. MATERIALS AND METHODS: We have developed an IMRT planning methodology to incorporate functional PET imaging using [(18)F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4>SUV3 ≥ 3; and 3 > SUV2 ≥ 2. Dose objectives were set to reduce bone marrow volume that received 10 (V(10)) and 20 (V(20))Gy. RESULTS: Active bone marrow regions identified by [(18)F]FLT with an SUV ≥ 2, SUV ≥ 3, and SUV ≥ 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V(10), and V(20) were achieved without clinically significant changes to PTV or OAR doses. CONCLUSIONS: Incorporation of [(18)F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.

3'-deoxy-3'-[¹8F]fluorothymidine PET quantification of bone marrow response to radiation dose.

PURPOSE: The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans. METHODS AND MATERIALS: Pre- and post-Week 1 treatment [(18)F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [(18)F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6-T7 vertebrae that straddled the field edge were measured for all patients. RESULTS: Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and <7 Gy were statistically significant (p < 0.01, two-sample t test). The reduction in SUV was approximately linear until it reached a reduction threshold of 75%-80% in SUV for doses greater than 6 Gy/week for both the dose-binned data and the vertebral maximum SUVs. CONCLUSIONS: The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [(18)F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [(18)F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

A methodology for using SPECT to reduce intensity-modulated radiation therapy (IMRT) dose to functioning lung.

PURPOSE: Single photon emission computed tomography (SPECT) provides a map of the spatial distribution of lung perfusion. Thus, SPECT guidance can be used to divert dose away from higher-functioning lung, potentially reducing lung toxicity. We present a methodology for achieving this aim and test it in intensity-modulated radiotherapy (IMRT) treatment-planning. METHODS AND MATERIALS: IMRT treatment plans were generated with and without SPECT guidance and compared for 5 patients. Healthy lung was segmented into four regions on the basis of SPECT intensity in the SPECT plan. Dose was sequentially allowed to the target via regions of increasing SPECT intensity. This process results in reduction of dose to functional lung, reflected in the dose-function histogram (DFH). The plans were compared using DFHs and F(20)/F(30) values (F(x) is the functional lung receiving dose above x Gy). RESULTS: In all cases, the SPECT-guided plan produced a more favorable DFH compared with the non-SPECT-guided plan. Additionally, the F(20) and F(30) values were reduced for all patients by an average of 13.6% +/- 5.2% and 10.5% +/- 5.8%, respectively. In all patients, DFHs of the two highest-functioning SPECT regions were reduced, whereas DFHs of the two lower-functioning regions were increased, illustrating the dose "give-take" between SPECT regions during redistribution. CONCLUSIONS: SPECT-guided IMRT shows potential for reducing the dose delivered to highly functional lung regions. This dose reduction could reduce the number of high-grade pneumonitis cases that develop after radiation treatment and improve patient quality of life.