In vivo Portal Imaging Dosimetry Identifies Delivery Errors in Rectal Cancer Radiotherapy on the Belly Board Device.

PURPOSE: We recently developed a novel, open-source in vivo dosimetry that uses the electronic portal imaging device to detect dose delivery discrepancies. We applied our method on patients with rectal cancer treated on a belly board device. METHODS: In vivo dosimetry was performed on 10 patients with rectal cancer treated prone on the belly board with a 4-field box arrangement. Portal images were acquired approximately once per week from each treatment beam. Our dosimetry method used these images along with the planning CT to reconstruct patient planar dose at isocenter depth. RESULTS: Our algorithm proved sensitive to dose discrepancies and detected discordances in 7 patients. The majority of these were due to soft tissue differences between planning and treatment, present despite matching to bony anatomy. As a result of this work, quality assurance procedures have been implemented for our immobilization devices. CONCLUSION: In vivo dosimetry is a powerful quality assurance tool that can detect delivery discrepancies, including changes in patient setup and position. The added information on actual dose delivery may be used to evaluate equipment and process quality and to guide for adaptive radiotherapy.

A Simple Method for 2-D In Vivo Dosimetry by Portal Imaging.

PURPOSE: To improve patient safety and treatment quality, verification of dose delivery in radiotherapy is desirable. We present a simple, easy-to-implement, open-source method for in vivo planar dosimetry of conformal radiotherapy by electronic portal imaging device (EPID). METHODS: Correlation ratios, which relate dose in the mid-depth of slab phantoms to transit EPID signal, were determined for multiple phantom thicknesses and field sizes. Off-axis dose is corrected for by means of model-based convolution. We tested efficacy of dose reconstruction through measurements with off-reference values of attenuator thickness, field size, and monitor units. We quantified the dose calculation error in the presence of thickness changes to simulate anatomical or setup variations. An example of dose calculation on patient data is provided. RESULTS: With varying phantom thickness, field size, and monitor units, dose reconstruction was almost always within 3% of planned dose. In the presence of thickness changes from planning CT, the dose discrepancy is exaggerated by up to approximately 1.5% for 1 cm changes upstream of the isocenter plane and 4% for 1 cm changes downstream. CONCLUSION: Our novel electronic portal imaging device in vivo dosimetry allows clinically accurate 2-dimensional reconstruction of dose inside a phantom/patient at isocenter depth. Due to its simplicity, commissioning can be performed in a few hours per energy and may be modified to the user's needs. It may provide useful dose delivery information to detect harmful errors, guide adaptive radiotherapy, and assure quality of treatment.

Identification of neurovascular changes associated with cerebral amyloid angiopathy from subject-specific hemodynamic response functions.

Cerebral amyloid angiopathy (CAA) is a small-vessel disease preferentially affecting posterior brain regions. Recent evidence has demonstrated the efficacy of functional MRI in detecting CAA-related neurovascular injury, however, it is unknown whether such perturbations are associated with changes in the hemodynamic response function (HRF). Here we estimated HRFs from two different brain regions from block design activation data, in light of recent findings demonstrating how block designs can accurately reflect HRF parameter estimates while maximizing signal detection. Patients with a diagnosis of probable CAA and healthy controls performed motor and visual stimulation tasks. Time-to-peak (TTP), full-width at half-maximum (FWHM), and area under the curve (AUC) of the estimated HRFs were compared between groups and to MRI features associated with CAA including cerebral microbleed (CMB) count. Motor HRFs in CAA patients showed significantly wider FWHM ( P = 0.006) and delayed TTP ( P = 0.03) compared to controls. In the patient group, visual HRF FWHM was positively associated with CMB count ( P = 0.03). These findings indicate that hemodynamic abnormalities in patients with CAA may be reflected in HRFs estimated from block designs across different brain regions. Moreover, visual FWHM may be linked to structural MR indications associated with CAA.

Two-dimensional in vivo dose verification using portal imaging and correlation ratios.

The electronic portal imaging device (EPID) has the potential to be used for in vivo dosimetry during radiation therapy as an additional dose delivery check. In this study we have extended a method developed by A. Piermattei and colleagues in 2006 that made use of EPID transit images (acquired during treatment) to calculate dose in the isocenter point. The extension allows calculation of two-dimensional dose maps of the entire radiation field at the depth of isocenter. We quantified the variability of the ratio of EPID signal to dose in the isocenter plane in Solid Water phantoms of various thicknesses and with various field sizes, and designed a field edge dose calculation correction. To validate the method, we designed three realistic conventional radiation therapy treatment plans on a thorax and head anthropomorphic phantom (whole brain, brain primary, lung tumor). Using CT data, EPID transit images, EPID signal-to-dose correlation, and our edge correction, we calculated dose in the isocenter plane and compared it with the treatment planning system's prediction. Gamma evaluation (3%, 3 mm) showed good agreement (Pγ<1 ≥ 96.5%) for all fields of the whole brain and brain primary plans. In the presence of lung, however, our algorithm overestimated dose by 7%-9%. This 2D EPID-based in vivo dosimetry method can be used for posttreatment dose verification, thereby improving the safety and quality of patient treatments. With future work, it may be extended to measure dose in real time and to prevent harmful delivery errors.

Effects of aging on the association between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness.

Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older = 106 ± 17%, p < 0.001) and systemic (young = 59 ± 9% and older = 80 ± 9%, p < 0.001) augmentation indices (AI) were higher in the older group. CBF responses to VS (PCA: p < 0.026) and hypercapnia (PCA: p = 0.018; MCA: p = 0.042) were lower in the older group. A curvilinear model fitted to cerebral AI and age showed AI increases until ~60 years of age, after which the increase levels off (PCA: R (2) = 0.45, p < 0.001; MCA: R (2) = 0.31, p < 0.001). Finally, MCA, but not PCA, hypercapnic reactivity was inversely related to cerebral AI (MCA: R (2) = 0.28, p = 0.002; PCA: R (2) = 0.10, p = 0.104). A similar inverse relationship was not observed with the PCA blood flow response to VS (R (2) = 0.06, p = 0.174). In conclusion, older subjects had reduced neurovascular- and hypercapnia-mediated CBF responses. Furthermore, lower hypercapnia-mediated blood flow responses through the MCA were associated with increased vascular stiffness. These findings suggest the reduced hypercapnia-evoked CBF responses through the MCA, in older individuals may be secondary to vascular stiffening.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. METHODS: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Metabolic correlatives of brain activity in a FOS epilepsy patient.

The correlation and the interactions between neuronal activity and underlying metabolic dynamics are still a matter of debate, especially in pathological conditions. This study reports findings obtained on a subject suffering from fixation-off sensitivity (FOS) epilepsy, exploited as a model system of triggerable anomalous electrical activity. Functional Magnetic Resonance Spectroscopy was used to investigate the metabolic response to visual spike-inducing stimuli in a single voxel placed in the temporo-occipital lobe of a FOS epilepsy patient. MRS measurements were additionally performed on a control group of five healthy volunteers. The FOS patient also underwent an EEG session with the same stimulus paradigm. Uniquely in the FOS patient, glutamate and glutamine concentration increased during the first 10 min of stimulation and then returned to baseline. On the other hand, FOS-induced epileptic activity (spiking) endured throughout all the stimulation epoch. The observed metabolic dynamics may be likely linked to a complex interplay between alterations of the metabolic pathways of glutamate and modulation of the neuronal activity.

Metabolic alteration transients during paroxysmal activity in an epileptic patient with fixation-off sensitivity: a case study.

The purpose of this study was to investigate short-time metabolic variations related to continuous epileptic activity elicited by fixation-off sensitivity (FOS). Time-resolved magnetic resonance spectroscopy was performed on a patient on whom previous clinical findings clearly indicated presence of FOS. The epileptic focus was localized with a simultaneous electroencephalographic and functional magnetic resonance imaging study. The results showed a linear increase of the sum of glutamate and glutamine with time of paroxysmal activity in epileptic focus and much greater concentration of choline-containing compounds in focus than in the contralateral side.