A test of the functional avoidance hypothesis in the development of overgeneral autobiographical memory.

Overgeneral memory (OGM) refers to the failure to recall memories of specific personally experienced events, which occurs in various psychiatric disorders. One pathway through which OGM is theorized to develop is the avoidance of thinking of negative experiences, whereby cumulative avoidance may maladaptively generalize to autobiographical memory (AM) more broadly. We tested this, predicting that negative experiences would interact with avoidance to predict AM specificity. In Study 1 (N = 281), negative life events (over six months) and daily hassles (over one month) were not related to AM specificity, nor was avoidance, and no interaction was found. In Study 2 (N = 318), we revised our measurements and used an increased timeframe of 12 months for both negative life events and daily hassles. The results showed no interaction effect for negative life events, but they did show an interaction for daily hassles, whereby increased hassles and higher avoidance of thinking about them were associated with reduced AM specificity, independent of general cognitive avoidance and depressive symptoms. No evidence was found that cognitive avoidance or AM specificity moderated the effect of negative experiences on depressive symptoms. Our findings suggest that life events over 6-12 months are not associated with AM specificity, but chronic daily hassles over 12 months predict reduced AM specificity when individuals avoid thinking about them. The findings provide evidence for the functional-avoidance hypothesis of OGM development and future directions for longitudinal studies.

Measuring Indirect Radiation-Induced Perfusion Change in Fed Vasculature Using Dynamic Contrast CT.

Recent functional lung imaging studies have presented evidence of an "indirect effect" on perfusion damage, where regions that are unirradiated or lowly irradiated but that are supplied by highly irradiated regions observe perfusion damage post-radiation therapy (RT). The purpose of this work was to investigate this effect using a contrast-enhanced dynamic CT protocol to measure perfusion change in five novel swine subjects. A cohort of five Wisconsin Miniature Swine (WMS) were given a research course of 60 Gy in five fractions delivered locally to a vessel in the lung using an Accuray Radixact tomotherapy system with Synchrony motion tracking to increase delivery accuracy. Imaging was performed prior to delivering RT and 3 months post-RT to yield a 28−36 frame image series showing contrast flowing in and out of the vasculature. Using MIM software, contours were placed in six vessels on each animal to yield a contrast flow curve for each vessel. The contours were placed as follows: one at the point of max dose, one low-irradiated (5−20 Gy) branching from the max dose vessel, one low-irradiated (5−20 Gy) not branching from the max dose vessel, one unirradiated (<5 Gy) branching from the max dose vessel, one unirradiated (<5 Gy) not branching from the max dose vessel, and one in the contralateral lung. Seven measurements (baseline-to-baseline time and difference, slope up and down, max rise and value, and area under the curve) were acquired for each vessel's contrast flow curve in each subject. Paired Student t-tests showed statistically significant (p < 0.05) reductions in the area under the curve in the max dose, and both fed contours indicating an overall reduction in contrast in these regions. Additionally, there were statistically significant reductions observed when comparing pre- and post-RT in slope up and down in the max dose, low-dose fed, and no-dose fed contours but not the low-dose not-fed, no-dose not-fed, or contralateral contours. These findings suggest an indirect damage effect where irradiation of the vasculature causes a reduction in perfusion in irradiated regions as well as regions fed by the irradiated vasculature.

Virtual bronchoscopy-guided lung SAbR: dosimetric implications of using AAA versus Acuros XB to calculate dose in airways.

In previous works, we showed that incorporating individual airways as organs-at-risk (OARs) in the treatment of lung stereotactic ablative radiotherapy (SAbR) patients potentially mitigates post-SAbR radiation injury. However, the performance of common clinical dose calculation algorithms in airways has not been thoroughly studied. Airways are of particular concern because their small size and the density differences they create have the potential to hinder dose calculation accuracy. To address this gap in knowledge, here we investigate dosimetric accuracy in airways of two commonly used dose calculation algorithms, the anisotropic analytical algorithm (AAA) and Acuros-XB (AXB), recreating clinical treatment plans on a cohort of four SAbR patients. A virtual bronchoscopy software was used to delineate 856 airways on a high-resolution breath-hold CT (BHCT) image acquired for each patient. The planning target volumes (PTVs) and standard thoracic OARs were contoured on an average CT (AVG) image over the breathing cycle. Conformal and intensity-modulated radiation therapy plans were recreated on the BHCT image and on the AVG image, for a total of four plan types per patient. Dose calculations were performed using AAA and AXB, and the differences in maximum and mean dose in each structure were calculated. The median differences in maximum dose among all airways were ≤0.3Gy in magnitude for all four plan types. With airways grouped by dose-to-structure or diameter, median dose differences were still ≤0.5Gy in magnitude, with no clear dependence on airway size. These results, along with our previous airway radiosensitivity works, suggest that dose differences between AAA and AXB correspond to an airway collapse variation ≤0.7% in magnitude. This variation in airway injury risk can be considered as not clinically relevant, and the use of either AAA or AXB is therefore appropriate when including patient airways as individual OARs so as to reduce risk of radiation-induced lung toxicity.

Synthetic pulmonary perfusion images from 4DCT for functional avoidance using deep learning.

Purpose.To develop and evaluate the performance of a deep learning model to generate synthetic pulmonary perfusion images from clinical 4DCT images for patients undergoing radiotherapy for lung cancer.Methods. A clinical data set of 58 pre- and post-radiotherapy99mTc-labeled MAA-SPECT perfusion studies (32 patients) each with contemporaneous 4DCT studies was collected. Using the inhale and exhale phases of the 4DCT, a 3D-residual network was trained to create synthetic perfusion images utilizing the MAA-SPECT as ground truth. The training process was repeated for a 50-imaging study, five-fold validation with twenty model instances trained per fold. The highest performing model instance from each fold was selected for inference upon the eight-study test set. A manual lung segmentation was used to compute correlation metrics constrained to the voxels within the lungs. From the pre-treatment test cases (N = 5), 50th percentile contours of well-perfused lung were generated from both the clinical and synthetic perfusion images and the agreement was quantified.Results. Across the hold-out test set, our deep learning model predicted perfusion with a Spearman correlation coefficient of 0.70 (IQR: 0.61-0.76) and a Pearson correlation coefficient of 0.66 (IQR: 0.49-0.73). The agreement of the functional avoidance contour pairs was Dice of 0.803 (IQR: 0.750-0.810) and average surface distance of 5.92 mm (IQR: 5.68-7.55).Conclusion. We demonstrate that from 4DCT alone, a deep learning model can generate synthetic perfusion images with potential application in functional avoidance treatment planning.

Characterizing spatial differences between SPECT-ventilation and SPECT-perfusion in patients with lung cancer undergoing radiotherapy.

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation-coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer.

BACKGROUND AND PURPOSE: Functional avoidance radiation therapy (RT) aims at sparing functional lung regions. The purpose of this simulation study was to evaluate the feasibility of functional lung avoidance methodology in RT of lung cancer and to characterize the achievable dosimetry of single photon emission computed tomography (SPECT) guided treatment planning. MATERIALS AND METHODS: Fifteen consecutive lung cancer patients were included and planned for definitive RT of 60-66 Gy in 2-Gy fractions. Two plans were optimized: a standard CT-plan, and functional SPECT-plan. The objective was to reduce dose to the highly functional lung subvolumes without compromising tumour coverage, and respecting dose to other organs at risk. For each patient a 3D-conformal, intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy plans were created for standard and functional avoidance. Standard versus functional dose-volume parameters for functional lung (FL) subvolumes, organs at risk and tumour coverage were compared. RESULTS: The largest dose reduction was achieved with IMRT plans. Functional plans resulted in dose reduction from 9.0 Gy to 6.7 Gy (mean reduction of 2.3 Gy or 26%) to the highest functional subvolume FL80% (95%CI 1.1; 3.5). Dose to FL40% was reduced from 13.3 Gy to 11.6 Gy with functional planning. Dose reduction to FL40% was 1.7 Gy (95%CI 0.9; 2.6). Functional volume of lung receiving over 20 Gy improved by 5% (standard 22%, functional 17%). Dose to organs at risk and tumour coverage were not significantly different between plans. CONCLUSIONS: SPECT/CT-guided planning resulted in improved dose-volumetric outcomes for functional lung. This methodology may lead to potential reduction in radiation-induced lung toxicity.

Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients.

PURPOSE: To evaluate the feasibility of a novel planning concept that differentially redistributes RT dose away from functional liver regions as defined by (99m)Tc-sulphur colloid (SC) uptake on patient SPECT/CT images. MATERIALS AND METHODS: Ten HCC patients with different Child-Turcotte-Pugh scores (A5-B9) underwent SC SPECT/CT scans in treatment position prior to RT that were registered to planning CT scans. Proton pencil beam scanning (PBS) therapy plans were optimized to deliver 37.5-60.0Gy (RBE) over 5-15 fractions using single field uniform dose technique robust to range and setup uncertainty. Photon volumetrically modulated arc therapy (VMAT) plans were optimized to the same prescribed dose and minimum target coverage. For both treatment modalities, differential hepatic avoidance RT (DHART) plans were generated to decrease dose to functional liver volumes (FLV) defined by a range of thresholds relative to maximum SC uptake (43-90%) in the tumor-subtracted liver. Radiation dose was redistributed away from regions of increased SC uptake in each FLV by linearly scaling mean dose objectives during PBS or VMAT optimization. DHART planning feasibility was assessed by a significantly negative Spearman's rank correlation (RS) between dose difference and SC uptake. Patient, tumor, and treatment planning characteristics were tested for association to DHART planning feasibility using non-parametric Kruskal-Wallis ANOVA. RESULTS: Compared to conventional plans, DHART plans achieved a 3% FLV dose reduction for every 10% SC uptake increase. DHART planning was feasible in the majority of patients with 60% of patients having RS<-0.5 (p<0.01, range -1.0 to 0.2) and was particularly effective in 30% of patients (RS<-0.9). Mean dose to FLV was reduced by up to 20% in these patients. Only fractionation regimen was associated with DHART planning feasibility: 15 fraction courses were more feasible than 5-6 fraction courses (RS<-0.93 vs. RS>-0.60, p<0.02). CONCLUSION: Differential avoidance of functional liver regions defined on sulphur colloid SPECT/CT is achievable with either photon VMAT or proton PBS therapy. Further investigation with phantom studies and in a larger cohort of patients may validate the utility of DHART planning for HCC radiotherapy.