Feasibility of Ultrasonic Heating through Skull Phantom Using Single-element Transducer.

Background: Noninvasive neurosurgery has become possible through the use of transcranial focused ultrasound (FUS). This study assessed the heating ability of single element spherically focused transducers operating at 0.4 and 1.1 MHz through three-dimensional (3D) printed thermoplastic skull phantoms. Methods: Phantoms with precise skull bone geometry of a male patient were 3D printed using common thermoplastic materials following segmentation on a computed tomography head scan image. The brain tissue was mimicked by an agar-based gel phantom developed in-house. The selection of phantom materials was mainly based on transmission-through attenuation measurements. Phantom sonications were performed through water, and then, with the skull phantoms intervening the beam path. In each case, thermometry was performed at the focal spot using thermocouples. Results: The focal temperature change in the presence of the skull phantoms was reduced to less than 20 % of that recorded in free field when using the 0.4 MHz transducer, whereas the 1.1 MHz trans-skull sonication produced minimal or no change in focal temperature. The 0.4 MHz transducer showed better performance in trans-skull transmission but still not efficient. Conclusion: The inability of both tested single element transducers to steer the beam through the high attenuating skull phantoms and raise the temperature at the focus was confirmed, underlying the necessity to use a correction technique to compensate for energy losses, such those provided by phased arrays. The proposed phantom could be used as a cost-effective and ergonomic tool for trans-skull FUS preclinical studies.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

A Survey of Greek Primary Care Physicians on Their Likeability in Treating Migraines and Other Common Diseases.

Background and objectives: Migraine is considered the most clinically important primary headache due to its high prevalence and significant burden. Although globally categorized as one of the leading causes of disability, it is still largely underdiagnosed and undertreated. Worldwide, migraine care is in most cases provided by primary care physicians. The aim of our study was to assess the attitudes of Greek primary care physicians toward treating migraine compared to other common neurological and general medical disorders. Methods: We surveyed 182 primary care physicians with the use of a 5-point questionnaire regarding their preference in treating ten common medical conditions, including migraine, hypertension, hyperlipidemia, upper respiratory tract infections, diabetes mellitus, lower back pain, dizziness, transient ischemic attack, diabetic peripheral neuropathy, and fibromyalgia. Results: Overall, with regards to preference to treat, migraine scored very low (3.6 ± 1.0), next to diabetic peripheral neuropathy (3.6 ± 1.0), and third from the bottom to fibromyalgia (3.25 ± 1.06). In contrast, physicians reported a much higher preference to treat hypertension (4.66 ± 0.60) and hyperlipidemia (4.6 ± 1.0). Conclusions: Our results indicate that Greek primary care physicians dislike treating migraines but also other neurological diseases. Topics for further investigation include the reasons for this dislike, any associations with poor patient satisfaction, treatment results, or both.

MR relaxation times of agar-based tissue-mimicking phantoms.

Agar gels were previously proven capable of accurately replicating the acoustical and thermal properties of real tissue and widely used for the construction of tissue-mimicking phantoms (TMPs) for focused ultrasound (FUS) applications. Given the current popularity of magnetic resonance-guided FUS (MRgFUS), we have investigated the MR relaxation times T1 and T2 of different mixtures of agar-based phantoms. Nine TMPs were constructed containing agar as the gelling agent and various concentrations of silicon dioxide and evaporated milk. An agar-based phantom doped with wood powder was also evaluated. A series of MR images were acquired in a 1.5 T scanner for T1 and T2 mapping. T2 was predominantly affected by varying agar concentrations. A trend toward decreasing T1 with an increasing concentration of evaporated milk was observed. The addition of silicon dioxide decreased both relaxation times of pure agar gels. The proposed phantoms have great potential for use with the continuously emerging MRgFUS technology. The MR relaxation times of several body tissues can be mimicked by adjusting the concentration of ingredients, thus enabling more accurate and realistic MRgFUS studies.

A comparative autopsy study of the injury distribution and severity between suicidal and accidental high falls.

Falls are the second cause of accidental deaths worldwide. Falls from height are also a common method of suicide. The aim of this study is to compare the characteristics of the victims, the circumstances of the fall and the severity and distribution of the injuries reported in an autopsy case series of falls from height. This study is a retrospective analysis of consecutive autopsy cases of suicidal and accidental falls from height which were investigated in the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens during the period 2011-2019. The recorded variables included demographic data of the victim, height of fall, length of hospital stay, toxicological results, the existence and location of injuries and Injury Severity Score (ISS). Victims of suicidal falls were younger (55.53 vs. 62.98, p = 0.001), they fell from higher heights (12.35 vs. 5.18 m, p < 0.001), and they sustained more severe injuries compared with victims of accidental falls (ISS 51.01 vs. 40.88, p < 0.001). Injuries in the thorax, abdomen, pelvis, upper and lower extremities were more frequently observed after a suicidal fall (93.6% vs. 67.3%, 72.1% vs. 21.4%, 72.1% vs. 27.6%, 42.9% vs. 15.3%, 45.7% vs. 13.3%, respectively-p < 0.001), probably due to the higher height of fall. Our study outlines the differences in the profile of the victims and in the severity of injuries caused by falls from height depending on the intention of the victim to fall. However, a distinctive injury pattern in victims of suicidal falls was not demonstrated.

Acoustical properties of 3D printed thermoplastics.

With focused ultrasound (FUS) gaining popularity as a therapeutic modality for brain diseases, the need for skull phantoms that are suitable for evaluating FUS protocols is increasing. In the current study, the acoustical properties of several three-dimensional (3D) printed thermoplastic samples were evaluated to assess their suitability to mimic human skull and bone accurately. Samples were 3D printed using eight commercially available thermoplastic materials. The acoustic properties of the printed samples, including attenuation coefficient, speed of sound, and acoustic impedance, were investigated using transmission-through and pulse-echo techniques. The ultrasonic attenuation, estimated at a frequency of 1.1 MHz, varied from approximately 7 to 32 dB/cm. The frequency dependence of attenuation was described by a power law in the frequency range of 0.2-3.5 MHz, and the exponential index of frequency was found to vary from 1.30 to 2.24. The longitudinal velocity of 2.7 MHz sound waves was in the range of 1700-3050 m/s. The results demonstrate that thermoplastics could potentially be used for the 3D construction of high-quality skull phantoms.

Ultrasonic Attenuation of an Agar, Silicon Dioxide, and Evaporated Milk Gel Phantom.

BACKGROUND: It has been demonstrated that agar-based gel phantoms can emulate the acoustic parameters of real tissues and are the most commonly used tissue-mimicking materials for high-intensity focused ultrasound applications. The following study presents ultrasonic attenuation measurements of agar-based phantoms with different concentrations of additives (percent of agar, silicon dioxide and evaporated milk) in an effort of matching the material's acoustic property as close as possible to human tissues. METHODS: Nine different agar-based phantoms with various amounts of agar, silicon dioxide, and evaporated milk were prepared. Attenuation measurements of the samples were conducted using the through-transmission immersion techniques. RESULTS: The ultrasonic attenuation coefficient of the agar-based phantoms varied in the range of 0.30-1.49 dB/cm-MHz. The attenuation was found to increase in proportion to the concentration of agar and evaporated milk. Silicon dioxide was found to significantly contribute to the attenuation coefficient up to 4% weight to volume (w/v) concentration. CONCLUSION: The acoustic attenuation coefficient of agar-based phantoms can be adjusted according to the tissue of interest in the range of animal and human tissues by the proper selection of agar, silicon dioxide, and evaporated milk.

MRI compatibility testing of commercial high intensity focused ultrasound transducers.

PURPOSE: The study aimed to compare the performance of eight commercially available single-element High Intensity Focused Ultrasound (HIFU) transducers in terms of Magnetic Resonance Imaging (MRI) compatibility. METHODS: Imaging of an agar-based MRI phantom was performed in a 3 T MRI scanner utilizing T2-Weighted Fast Spin Echo (FSE) and Fast low angle shot (FLASH) sequences, which are typically employed for high resolution anatomical imaging and thermometry, respectively. Reference magnitude and phase images of the phantom were compared with images acquired in the presence of each transducer in terms of the signal to noise ratio (SNR), introduced artifacts, and overall image quality. RESULTS: The degree of observed artifacts highly differed among the various transducers. The transducer whose backing material included magnetic impurities showed poor performance in the MRI, introducing significant susceptibility artifacts such as geometric distortions and signal void bands. Additionally, it caused the most significant SNR drop. Other transducers were shown to exhibit high level of MRI compatibility as the resulting images closely resembled the reference images with minimal to no apparent artifacts and comparable SNR values. CONCLUSIONS: The study findings may facilitate researchers to select the most suitable transducer for their research, simultaneously avoiding unnecessary testing. The study further provides useful design considerations for MRI compatible transducers.

A Magnetic Resonance Spectroscopy Study on Polarity Subphenotypes in Bipolar Disorder.

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

Simple, inexpensive, and ergonomic phantom for quality assurance control of MRI guided Focused Ultrasound systems.

PURPOSE: The popularity of Magnetic Resonance guided Focused Ultrasound (MRgFUS) as a beneficial therapeutic solution for many diseases is increasing rapidly, thus raising the need for reliable quality assurance (QA) phantoms for routine testing of MRgFUS systems. In this study, we propose a thin acrylic film as the cheapest and most easily accessible phantom for assessing the functionality of MRgFUS hardware and software. METHODS: Through the paper, specific QA tests are detailed in the framework of evaluating an MRgFUS preclinical robotic device comprising a single element spherically focused transducer with a nominal frequency of 2.75 MHz. These tests take advantage of the reflection of ultrasonic waves at a plastic-air interface, which results in almost immediate lesion formation on the film at a threshold of applied acoustic energy. RESULTS: The phantom offered qualitative information on the power field distribution of the FUS transducer and the ability to visualize different FUS protocols. It also enabled quick and reliable assessment of various navigation algorithms as they are used in real treatments, and also allowed for the assessment of the accuracy of robotic motion. CONCLUSION: Therefore, it could serve as a useful tool for detecting defects in system's performance over its lifetime after establishing a baseline while concurrently contributing to establish QA and calibration guidelines for clinical routine controls.

Preclinical robotic device for magnetic resonance imaging guided focussed ultrasound.

BACKGROUND: A robotic device featuring three motion axes was manufactured for preclinical research on focussed ultrasound (FUS). The device comprises a 2.75 MHz single element ultrasonic transducer and is guided by Magnetic Resonance Imaging (MRI). METHODS: The compatibility of the device with the MRI was evaluated by estimating the influence on the signal-to-noise ratio (SNR). The efficacy of the transducer in generating ablative temperatures was evaluated in phantoms and excised porcine tissue. RESULTS: System's activation in the MRI scanner reduced the SNR to an acceptable level without compromising the image quality. The transducer demonstrated efficient heating ability as proved by MR thermometry. Discrete and overlapping thermal lesions were inflicted in excised tissue. CONCLUSIONS: The FUS system was proven effective for FUS thermal applications in the MRI setting. It can thus be used for multiple preclinical applications of the emerging MRI-guided FUS technology. The device can be scaled-up for human use with minor modifications.

Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer.

PURPOSE: The study aims to provide insights on the practicality of using single-element transducers for transcranial Focused Ultrasound (tFUS) thermal applications. METHODS: FUS sonications were performed through skull phantoms embedding agar-based tissue mimicking gels using a 1 MHz single-element spherically focused transducer. The skull phantoms were 3D printed with Acrylonitrile Butadiene Styrene (ABS) and Resin thermoplastics having the exact skull bone geometry of a healthy volunteer. The temperature field distribution during and after heating was monitored in a 3 T Magnetic Resonance Imaging (MRI) scanner using MR thermometry. The effect of the skull's thickness on intracranial heating was investigated. RESULTS: A single FUS sonication at focal acoustic intensities close to 1580 W/cm2 for 60 s in free field heated up the agar phantom to ablative temperatures reaching about 90 °C (baseline of 37 °C). The ABS skull strongly blocked the ultrasonic waves, resulting in zero temperature increase within the phantom. Considerable heating was achieved through the Resin skull, but it remained at hyperthermia levels. Conversely, tFUS through a 1 mm Resin skull showed enhanced ultrasonic penetration and heating, with the focal temperature reaching 70 °C. CONCLUSIONS: The ABS skull demonstrated poorer performance in terms of tFUS compared to the Resin skull owing to its higher ultrasonic attenuation and porosity. The thin Resin phantom of 1 mm thickness provided an efficient acoustic window for delivering tFUS and heating up deep phantom areas. The results of such studies could be particularly useful for accelerating the establishment of a wider range of tFUS applications.

Treatment of mammary cancer with focused ultrasound: A pilot study in canine and feline patients.

In recent years, veterinary medicine has expanded its practices beyond conventional methods, gradually integrating the Focused Ultrasound (FUS) technology in the care of companion animals like dogs and cats. The current study aimed to examine the feasibility and provide insights into the application of thermal FUS in canine and feline mammary cancer therapy. FUS was delivered by a 2-MHz single-element spherically focused ultrasonic transducer as integrated with an existing robotic positioning device. The functionality of the FUS system and sonication protocol in efficiently and safely ablating live tissue was initially validated in a rabbit thigh model in a laboratory environment. Nine (9) dogs and cats with superficial mammary cancer were recruited through a dedicated campaign according to specific safety criteria. The veterinary patients underwent FUS ablation followed by immediate surgical resection of the entire malignancy. Histopathology examination demonstrated well-defined regions of coagulative necrosis in all treated tumors with no off-target damage. Further study with a larger patient population is needed to confirm the current findings and demonstrate the safety and feasibility of complete FUS ablation of deep-seated tumors.

Development of an US, MRI, and CT imaging compatible realistic mouse phantom for thermal ablation and focused ultrasound evaluation.

Tissue mimicking phantoms (TMPs) play an essential role in modern biomedical research as cost-effective quality assurance and training tools, simultaneously contributing to the reduction of animal use. Herein, we present the development and evaluation of an anatomically accurate mouse phantom intended for image-guided thermal ablation and Focused Ultrasound (FUS) applications. The proposed mouse model consists of skeletal and soft tissue mimics, whose design was based on the Computed tomography (CT) scans data of a live mouse. Advantageously, it is compatible with US, CT, and Magnetic Resonance Imaging (MRI). The compatibility assessment was focused on the radiological behavior of the phantom due to the lack of relevant literature. The X-ray linear attenuation coefficient of candidate materials was estimated to assess the one that matches best the radiological behavior of living tissues. The bone part was manufactured by Fused Deposition Modeling (FDM) printing using Acrylonitrile styrene acrylate (ASA) material. For the soft-tissue mimic, a special mold was 3D printed having a cavity with the unique shape of the mouse body and filled with an agar-based silica-doped gel. The mouse phantom accurately matched the size and reproduced the body surface of the imaged mouse. Tissue-equivalency in terms of X-ray attenuation was demonstrated for the agar-based soft-tissue mimic. The phantom demonstrated excellent MRI visibility of the skeletal and soft-tissue mimics. Good radiological contrast between the skeletal and soft-tissue models was also observed in the CT scans. The model was also able to reproduce realistic behavior during trans-skull sonication as proved by thermocouple measurements. Overall, the proposed phantom is inexpensive, ergonomic, and realistic. It could constitute a powerful tool for image-guided thermal ablation and FUS studies in terms of testing and optimizing the performance of relevant equipment and protocols. It also possess great potential for use in transcranial FUS applications, including the emerging topic of FUS-mediated blood brain barrier (BBB) disruption.

Tumor phantom model for MRI-guided focused ultrasound ablation studies.

BACKGROUND: The persistent development of focused ultrasound (FUS) thermal therapy in the context of oncology creates the need for tissue-mimicking tumor phantom models for early-stage experimentation and evaluation of relevant systems and protocols. PURPOSE: This study presents the development and evaluation of a tumor-bearing tissue phantom model for testing magnetic resonance imaging (MRI)-guided FUS (MRgFUS) ablation protocols and equipment based on MR thermometry. METHODS: Normal tissue was mimicked by a pure agar gel, while the tumor simulator was differentiated from the surrounding material by including silicon dioxide. The phantom was characterized in terms of acoustic, thermal, and MRI properties. US, MRI, and computed tomography (CT) images of the phantom were acquired to assess the contrast between the two compartments. The phantom's response to thermal heating was investigated by performing high power sonications with a 2.4 MHz single element spherically focused ultrasonic transducer in a 3T MRI scanner. RESULTS: The estimated phantom properties fall within the range of literature-reported values of soft tissues. The inclusion of silicon dioxide in the tumor material offered excellent tumor visualization in US, MRI, and CT. MR thermometry revealed temperature elevations in the phantom to ablation levels and clear evidence of larger heat accumulation within the tumor owing to the inclusion of silicon dioxide. CONCLUSION: Overall, the study findings suggest that the proposed tumor phantom model constitutes a simple and inexpensive tool for preclinical MRgFUS ablation studies, and potentially other image-guided thermal ablation applications upon minimal modifications.

FUS-mediated blood-brain barrier disruption for delivering anti-Aß antibodies in 5XFAD Alzheimer's disease mice.

PURPOSE: Amyloid-ß (Aß) peptides, the main component of amyloid plaques found in the Alzheimer's disease (AD) brain, are implicated in its pathogenesis, and are considered a key target in AD therapeutics. We herein propose a reliable strategy for non-invasively delivering a specific anti-Aß antibody in a mouse model of AD by microbubbles-enhanced Focused Ultrasound (FUS)-mediated Blood-brain barrier disruption (BBBD), using a simple single stage MR-compatible positioning device. METHODS: The initial experimental work involved wild-type mice and was devoted to selecting the sonication protocol for efficient and safe BBBD. Pulsed FUS was applied using a single-element FUS transducer of 1 MHz (80 mm radius of curvature and 50 mm diameter). The success and extent of BBBD were assessed by Evans Blue extravasation and brain damage by hematoxylin and eosin staining. 5XFAD mice were divided into different subgroups; control (n = 1), FUS + MBs alone (n = 5), antibody alone (n = 5), and FUS + antibody combined (n = 10). The changes in antibody deposition among groups were determined by immunohistochemistry. RESULTS: It was confirmed that the antibody could not normally enter the brain parenchyma. A single treatment with MBs-enhanced pulsed FUS using the optimized protocol (1 MHz, 0.5 MPa in-situ pressure, 10 ms bursts, 1% duty factor, 100 s duration) transiently disrupted the BBB allowing for non-invasive antibody delivery to amyloid plaques within the sonicated brain regions. This was consistently reproduced in ten mice. CONCLUSION: These preliminary findings should be confirmed by longer-term studies examining the antibody effects on plaque clearance and cognitive benefit to hold promise for developing disease-modifying anti-Aß therapeutics for clinical use.

Phantom-based assessment of motion and needle targeting accuracy of robotic devices for magnetic resonance imaging-guided needle biopsy.

BACKGROUND: The current study proposes simple methods for assessing the performance of robotic devices intended for Magnetic Resonance Imaging (MRI)-guided needle biopsy. METHODS: In-house made agar-based breast phantoms containing biopsy targets served as the main tool in the evaluation process of an MRI compatible positioning device comprising a needle navigator. The motion accuracy of mechanical stages was assessed by calliper measurements. Laboratory evaluation of needle targeting included a repeatability phantom test and a laser-based method. The accuracy and repeatability of needle targeting was also assessed by MRI. RESULTS: The maximum error of linear motion for steps up to 10 mm was 0.1 mm. Needle navigation relative to the phantom and alignment with the various biopsy targets were performed successfully in both the laboratory and MRI settings. The proposed biopsy phantoms offered tissue-like signal in MRI and good haptic feedback during needle insertion. CONCLUSIONS: The proposed methods could be valuable in the process of validating the accuracy of MRI-guided biopsy robotic devices in both laboratory and real environments.

Predominant polarity as a neurobiological specifier in bipolar disorder: Evidence from a multimodal neuroimaging study.

BACKGROUND: While predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts. METHODS: Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons. RESULTS: Phenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an "unspecified" pattern mostly lying in-between PP-D and PP-M. CONCLUSIONS: Our multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD.