Subanesthetic S-ketamine does not acutely alter striatal dopamine transporter binding in healthy Sprague Dawley female rats.

Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have a slow onset of action, and 30% of patients show no clinically significant treatment response. The recently approved fast-acting antidepressant S-ketamine, an N-methyl-D-aspartate receptor antagonist, provides a new approach for treatment-resistant patients. However, knowledge of S-ketamine's mechanism of action is still being established. Depressed human subjects have lower striatal dopamine transporter (DAT) availability compared to healthy controls. Rodent studies report increased striatal dopamine concentration in response to acute ketamine administration. In vivo [18F]FE-PE2I ([18F]-(E)-N-(3-iodoprop-2-enyl)-2ß-carbofluoroethoxy-3ß-(4'-methyl-phenyl) nortropane) positron emission tomography (PET) imaging of the DAT has not previously been applied to assess the effect of acute subanesthetic S-ketamine administration on DAT availability. We applied translational in vivo [18F]FE-PE2I PET imaging of the DAT in healthy female rats to evaluate whether an acute subanesthetic intraperitoneal dose of 15 mg/kg S-ketamine alters DAT availability. We also performed [3H]GBR-12935 autoradiography on postmortem brain sections. We found no effect of acute S-ketamine administration on striatal DAT binding using [18F]FE-PE2I PET or [3H]GBR-12935 autoradiography. This negative result does not support the hypothesis that DAT changes are associated with S-ketamine's rapid antidepressant effects, but additional studies are warranted.

A simple method to measure the gating latencies in photon and proton based radiotherapy using a scintillating crystal.

BACKGROUND: In respiratory gated radiotherapy, low latency between target motion into and out of the gating window and actual beam-on and beam-off is crucial for the treatment accuracy. However, there is presently a lack of guidelines and accurate methods for gating latency measurements. PURPOSE: To develop a simple and reliable method for gating latency measurements that work across different radiotherapy platforms. METHODS: Gating latencies were measured at a Varian ProBeam (protons, RPM gating system) and TrueBeam (photons, TrueBeam gating system) accelerator. A motion-stage performed 1 cm vertical sinusoidal motion of a marker block that was optically tracked by the gating system. An amplitude gating window was set to cover the posterior half of the motion (0-0.5 cm). Gated beams were delivered to a 5 mm cubic scintillating ZnSe:O crystal that emitted visible light when irradiated, thereby directly showing when the beam was on. During gated beam delivery, a video camera acquired images at 120 Hz of the moving marker block and light-emitting crystal. After treatment, the block position and crystal light intensity were determined in all video frames. Two methods were used to determine the gate-on (τon ) and gate-off (τoff ) latencies. By method 1, the video was synchronized with gating log files by temporal alignment of the same block motion recorded in both the video and the log files. τon was defined as the time from the block entered the gating window (from gating log files) to the actual beam-on as detected by the crystal light. Similarly, τoff was the time from the block exited the gating window to beam-off. By method 2, τon and τoff were found from the videos alone using motion of different sine periods (1-10 s). In each video, a sinusoidal fit of the block motion provided the times Tmin of the lowest block position. The mid-time, Tmid-light , of each beam-on period was determined as the time halfway between crystal light signal start and end. It can be shown that the directly measurable quantity Tmid-light - Tmin  = (τoff +τon )/2, which provided the sum (τoff +τon ) of the two latencies. It can also be shown that the beam-on (i.e., crystal light) duration ΔTlight increases linearly with the sine period and depends on τoff - τon : ΔTlight  = constant•period+(τoff - τon ). Hence, a linear fit of ΔTlight as a function of the period provided the difference of the two latencies. From the sum (τoff +τon ) and difference (τoff - τon ), the individual latencies were determined. RESULTS: Method 1 resulted in mean (±SD) latencies of τon  = 255 ± 33 ms, τoff  = 82 ± 15 ms for the ProBeam and τon  = 84 ± 13 ms, τoff  = 44 ± 11 ms for the TrueBeam. Method 2 resulted in latencies of τon  = 255 ± 23 ms, τoff  = 95 ± 23 ms for the ProBeam and τon  = 83 ± 8 ms, τoff  = 46 ± 8 ms for the TrueBeam. Hence, the mean latencies determined by the two methods agreed within 13 ms for the ProBeam and within 2 ms for the TrueBeam. CONCLUSIONS: A novel, simple and low-cost method for gating latency measurements that work across different radiotherapy platforms was demonstrated. Only the TrueBeam fully fulfilled the AAPM TG-142 recommendation of maximum 100 ms latencies.

Intrafraction tumor motion monitoring and dose reconstruction for liver pencil beam scanning proton therapy.

Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D 2 %  -  D 98 % D 50 %   × 100 % . Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.

Evaluation of setup and intrafraction motion for surface guided whole-breast cancer radiotherapy.

Surface Guided Radiotherapy (SGRT) is a relatively new technique for positioning patients and for monitoring patient movement during treatment. SGRT is completely non-invasive since it uses visible light for determining the position of the patient surface. A reduction in daily imaging for patient setup is possible if the accuracy of SGRT is comparable to imaging. It allows for monitoring of intrafraction motion and the radiation beam can be held beyond a certain threshold resulting in a more accurate irradiation. The purpose of this study was to investigate setup uncertainty and the intrafraction motion in non-gated whole breast cancer radiotherapy treatment using an integrated implementation of AlignRT (OSMS) system as SGRT. In initial setup, SGRT was compared to three-point setup using tattoos on the patient and orthogonal kV imaging. For the investigation of intrafraction motion, OSMS monitored the patient with six degrees of freedom during treatment. Using three-point setup resulted in a setup root-mean-square error from the isocenter of 5.4 mm. This was improved to 4.2 mm using OSMS. For the translational directions, OSMS showed improvements in the lateral direction (P = 0.0009, Wilcoxon rank-sum), but for the longitudinal direction and rotation it was not possible to show improvements (P = 0.96 and P = 0.46, respectively). The vertical direction proved more accurate for three-point setup than OSMS (P = 0.000004). Intrafraction motion was very limited with a translational median of 1.1 mm from the isocenter. While OSMS showed marked improvements over laser and tattoo setup, the system did not prove accurate enough to replace the daily orthogonal kV images aligned to bony anatomy.

Advanced dose calculation algorithms in lung cancer radiotherapy: Implications for SBRT and locally advanced disease in deep inspiration breath hold.

PURPOSE: Evaluating performance of modern dose calculation algorithms in SBRT and locally advanced lung cancer radiotherapy in free breathing (FB) and deep inspiration breath hold (DIBH). METHODS: For 17 patients with early stage and 17 with locally advanced lung cancer, a plan in FB and in DIBH were generated with Anisotropic Analytical Algorithm (AAA). Plans for early stage were 3D-conformal SBRT, 45 Gy in 3 fractions, prescribed to 95% isodose covering 95% of PTV and aiming for 140% dose centrally in the tumour. Locally advanced plans were volumetric modulated arc therapy, 66 Gy in 33 fractions, prescribed to mean PTV dose. Calculation grid size was 1 mm for SBRT and 2.5 mm for locally advanced plans. All plans were recalculated with AcurosXB with same MU as in AAA, for comparison on target coverage and dose to risk organs. RESULTS: Lung volume increased in DIBH, resulting in decreased lung density (6% for early and 13% for locally-advanced group). In SBRT, AAA overestimated mean and near-minimum PTV dose (p-values < 0.01) compared to AcurosXB, with largest impact in DIBH (differences of up to 11 Gy). These clinically relevant differences may be a combination of small targets and large dose gradients within the PTV. In locally advanced group, AAA overestimated mean GTV, CTV and PTV doses by median less than 0.8 Gy and near-minimum doses by median 0.4-2.7 Gy. No clinically meaningful difference was observed for lung and heart dose metrics between the algorithms, for both FB and DIBH. CONCLUSIONS: AAA overestimated target coverage compared to AcurosXB, especially in DIBH for SBRT.

Urethra sparing - potential of combined Nickel-Titanium stent and intensity modulated radiation therapy in prostate cancer.

BACKGROUND AND PURPOSE: To investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model. MATERIALS AND METHODS: This theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel-Titanium (Ni-Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose. RESULTS: The feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability. CONCLUSIONS: A new concept for urethra dose reduction is presented. The method relies on the use of a Ni-Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control.