Evaluation of needle displacement errors in ultraosund-based brachytherapy using electromagnetic (EM) tracking

PurposeBy measuring the discrepancy of distance in electromagnetic tracking (EM) versus ultrasound images to calculate an error due to speed of sound (SOS) variances, this work establishes correctional values for inputs into post processing algorithms that will provide a correction based on B-Mode ultrasound images and consequently radiation dose plans in brachytherapy procedures. BackgroundThe speed of sound (SOS) within the soft tissue category is approximated to be 1540 m/s [1]. This fixed value is used for the SOS despite actual ranges in vivo varying considerably with one study measuring values of 1450 to 1613m/s in the field of view (FOV) [2]. The current state of technology doesn’t include a reasonable method for a patient-specific recalibration. Furthermore, inaccurate assignment of acoustic velocity may result in speed displacement and dispersion artifacts, especially at organ boundaries [2]. Brachytherapy for prostate cancer utilizes a transrectal ultrasound (TRUS) probe , which can provide 300-500 micron spatial resolution images for anatomical reference during needle implantation; however, the local composition and configuration of this soft tissue anatomy may exhibit a range of SOSs within the imaging field [3]. Images acquired with a SOS based on 1540 m/s and used in conjunction with stereotactic external coordinate systems can cause image distortion and displacement errors of several millimeters. In combination with the steep 1/r2 dose falloff around radioactive seeds, this can lead to erroneous dose delivery [4, 5]. Previous studies have outlined accuracy of 3-6 mm, leaving ample space for future robotics to overtake the manual process of seed implantation [6].Method & MaterialsThe Aurora EM tracking system (NDI Waterloo, Ontario, Canada) generates a 500mm x 500mm x 500mm local electromagnetic (EM) field which can detect the spatial location and orientation of sensors placed within. Philips (Amsterdam, The Netherlands) has developed a brachytherapy needle with an embedded sensor that produces a signal in the EM coordinate system. Results Using custom-built phantoms with SOS ranging between 1430 and 1530 m/s, EM tracking resolution was verified to <1 mm precision while US localization resulted in up to 3 mm displacements from physical measurement. We present a model of correction to mitigate error in needle trajectories due to SOS variances and using these values a correctional system will be demonstrated to show the effects of changes in dosimetry due to patient specific SOS variances in the prostate. Results show SOS measurements to be within 1% of measured using a water tank system. ConclusionPrevious studies have demonstrated that correct speed through tissue can be corrected, but may involve ionizing radiation or physical reference for these corrections [2,7]. The technique proposed will provide a new input of data, derived from the EM modality to approximate a more accurate SOS and result in an evaluation of accuracy of current clinically used systems

Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease

Older HIV-infected patients are at risk for both HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease. We investigated neuroimaging and neuropsychological performance of 61 virally suppressed older adults with HAND (mean (SD) age 64.3 (3.9) years), 53 demographically matched individuals with mild cognitive impairment of the Alzheimer's type (MCI-AD; 65.0 [4.8]), and 89 healthy controls (65.0 [4.3]) cross-sectionally and over 20 months. At the baseline, both disease groups exhibited lower volumes in multiple cortical and subcortical regions compared with controls. Hippocampal volume differentiated MCI-AD from HAND. Cognitively, MCI-AD performed worse on memory and language compared with HAND. Adjusted longitudinal models revealed greater diffuse brain atrophy in MCI-AD compared with controls, whereas HAND showed greater atrophy in frontal gray matter and cerebellum compared with controls. Comparing HAND with MCI-AD showed similar atrophy rates in all brain regions explored, with no significant findings. MCI-AD exhibited more pronounced language decline compared with HAND. These findings reveal the need for further work on unique cognitive phenotypes and neuroimaging signatures of HAND compared with early AD, providing preliminary clinical insight for differential diagnosis of age-related brain dysfunction in geriatric neuroHIV

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

BackgroundCurrent HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants.MethodsWe examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24).ResultsThe mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status.ConclusionsDespite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences

Structural and Functional Brain Imaging in Acute HIV

Background:HIV RNA is identified in cerebrospinalfluid (CSF) within eightdays of estimated viral exposure. Neurological findings and impaired neuropsychological testing performance are documented in a subset of individuals with acuteHIV infection (AHI). The purpose of this study was to determine whether microstructural white matter and resting-state functional connectivity (rsFC) are disruptedin AHI.Methods:We examined 49 AHI (100% male; mean age = 30 ± SD 9.9) and 23 HIV-uninfected Thai participants (78% male; age = 30 ± 5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four neuropsychological tests (summarized as NPZ-4). MRI for the AHI group was performed prior to combination antiretroviral treatment (ART) in 26 participants and on average two days (range:1–5) after ART in 23 participants. Fractional anisotropy (FA), mean (MD), axial(AD), and radial diffusivity (RD) were quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the default mode (DMN), fronto-parietal, and salience and 6 subcortical networks. rsFC and DTI analyses were corrected for family-wise error, with voxelwise comparisons completed using t-tests. Group-specific voxelwise regressions were conducted to examine relationships between imaging indices, HIV disease variables, and treatment status.Results:The AHI group had a mean (SD) CD4 count of 421(234) cells/mm3 plasma HIV RNA of 6.07(1.1) log10copies/mL and estimated duration of infection of20(5.5) days. Differences between AHI and CO groups did not meet statistical significance for DTI metrics. Within the AHI group, voxelwise analyses revealed associations between brief exposure to ART and higher FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and superior longitudinal fasciculus (p \u3c 0.05). Diffusion indices were unrelated to clinical variables or NPZ-4. The AHI group had reduced rsFC between left parahippocampal cortex (PHC)of the DMN and left middle frontal gyrus compared to CO (p \u3c 0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4 cell count associated with increased rsFC for the right lateral parietal and PHC seeds in the DMN. Direct associations were noted between NPZ-4 correspond to higher rsFC of the bilateral caudate seed (p \u3c 0.002).Conclusions: Study findings reveal minimal disruption to structural and functional brain integrity in the earliest stages of HIV. Longitudinal studies are needed to determine if treatment with ART initiated in AHI is sufficient to prevent the evolution of brain dysfunction identified in chronically infected individuals

Structural and Functional Brain Imaging in Acute HIV

Background: HIV RNA is identified in cerebrospinal fluid (CSF) within eight days of estimated viral exposure. Neurological findings and impaired neuropsychological testing performance are documented in a subset of individuals with acute HIV infection (AHI). The purpose of this study was to determine whether microstructural white matter and resting-state functional connectivity (rsFC) are disrupted in AHI.Methods: We examined 49 AHI (100% male; mean age = 30 ± SD 9.9) and 23 HIV-uninfected Thai participants (78% male; age = 30 ± 5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four neuropsychological tests (summarized as NPZ-4). MRI for the AHI group was performed prior to combination antiretroviral treatment (ART) in 26 participants and on average two days (range:1–5) after ART in 23 participants. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the default mode (DMN), fronto-parietal, and salience and 6 subcortical networks. rsFC and DTI analyses were corrected for family-wise error, with voxelwise comparisons completed using t-tests. Group-specific voxelwise regressions were conducted to examine relationships between imaging indices, HIV disease variables, and treatment status.Results: The AHI group had a mean (SD) CD4 count of 421(234) cells/mm3 plasma HIV RNA of 6.07(1.1) log10 copies/mL and estimated duration of infection of 20(5.5) days. Differences between AHI and CO groups did not meet statistical significance for DTI metrics. Within the AHI group, voxelwise analyses revealed associations between brief exposure to ART and higher FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and superior longitudinal fasciculus (p \u3c 0.05). Diffusion indices were unrelated to clinical variables or NPZ-4. The AHI group had reduced rsFC between left parahippocampal cortex (PHC) of the DMN and left middle frontal gyrus compared to CO (p \u3c 0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4 cell count associated with increased rsFC for the right lateral parietal and PHC seeds in the DMN. Direct associations were noted between NPZ-4 correspond to higher rsFC of the bilateral caudate seed (p \u3c 0.002).Conclusions: Study findings reveal minimal disruption to structural and functional brain integrity in the earliest stages of HIV. Longitudinal studies are needed to determine if treatment with ART initiated in AHI is sufficient to prevent the evolution of brain dysfunction identified in chronically infected individuals

Resting-state neural signatures of depressive symptoms in acute HIV

Depressive symptoms are often elevated in acute and chronic HIV. Previous neuroimaging research identifies abnormalities in emotion-related brain regions in depression without HIV, including the anterior cingulate cortex (ACC) and amygdala. However, no studies have examined the neural signatures of depressive symptoms in acute HIV infection (AHI). Seed-based voxelwise resting-state functional connectivity (rsFC) for affective seed regions of interest (pregenual ACC, subgenual ACC [sgACC], bilateral amygdala) was computed for 74 Thai males with AHI and 30 Thai HIV-uninfected controls. Group analyses compared rsFC of ACC and amygdala seed regions between AHI and uninfected control groups. Within the AHI group, voxelwise regression analyses investigated the relationship between depressive symptoms and rsFC for these affective seed regions. Group analyses revealed alterations in rsFC of the amygdala in AHI versus uninfected controls. Depressive symptoms associated with decreased rsFC between ACC regions and posterior cingulate/precuneus, medial temporal, and lateral parietal regions in AHI. Symptoms of depression also correlated to increased rsFC between ACC regions and lateral prefrontal cortex, sgACC, and cerebellum in AHI. Similar to the ACC, depressive symptoms associated with decreased rsFC between amygdala and precuneus. Of blood biomarkers, only HIV RNA inversely correlated with rsFC between posterior sgACC and left uncus. We found that depressive symptoms in AHI associate with altered rsFC of ACC and amygdala regions previously implicated in depression. Longitudinal research in this cohort will be necessary to determine whether these early alterations in rsFC of affective network regions are related to persistent depressive symptoms after combination antiretroviral therapy