Clinical Application and Further Development of Augmented Reality Guidance for the Surgical Localization of Pediatric Chest Wall Tumors.

BACKGROUND: Surgical treatment of pediatric chest wall tumors requires accurate surgical planning and tumor localization to achieve radical resections while sparing as much healthy tissue as possible. Augmented Reality (AR) could facilitate surgical decision making by improving anatomical understanding and intraoperative tumor localization. We present our clinical experience with the use of an AR system for intraoperative tumor localization during chest wall resections. Furthermore, we present the pre-clinical results of a new registration method to improve our conventional AR system. METHODS: From January 2021, we used the HoloLens 2 for pre-incisional tumor localization during all chest wall resections inside our center. A patient-specific 3D model was projected onto the patient by use of a five-point registration method based on anatomical landmarks. Furthermore, we developed and pre-clinically tested a surface matching method to allow post-incisional AR guidance by performing registration on the exposed surface of the ribs. RESULTS: Successful registration and holographic overlay were achieved in eight patients. The projection seemed most accurate when landmarks were positioned in a non-symmetric configuration in proximity to the tumor. Disagreements between the overlay and expected tumor location were mainly due to user-dependent registration errors. The pre-clinical tests of the surface matching method proved the feasibility of registration on the exposed ribs. CONCLUSIONS: Our results prove the applicability of AR guidance for the pre- and post-incisional localization of pediatric chest wall tumors during surgery. The system has the potential to enable intraoperative 3D visualization, hereby facilitating surgical planning and management of chest wall resections. LEVEL OF EVIDENCE: IV TYPE OF STUDY: Treatment Study.

3-D and 2-D reconstruction of bladders for the assessment of inter-session detection of tissue changes: a proof of concept.

PURPOSE: Abnormalities in the bladder wall require careful investigation regarding type, spatial position and invasiveness. Construction of a 3-D model of the bladder is helpful to ensure adequate coverage of the scanning procedure, quantitative comparison of bladder wall textures between successive sessions and finding back previously discovered abnormalities. METHODS: Videos of both an in vivo bladder and a textured bladder phantom were acquired. Structure-from-motion and bundle adjustment algorithms were used to construct a 3-D point cloud, approximate it by a surface mesh, texture it with the back-projected camera frames and draw the corresponding 2-D atlas. Reconstructions of successive sessions were compared; those of the bladder phantom were co-registered, transformed using 3-D thin plate splines and post-processed to highlight significant changes in texture. RESULTS: The reconstruction algorithms of the presented workflow were able to construct 3-D models and corresponding 2-D atlas of both the in vivo bladder and the bladder phantom. For the in vivo bladder the portion of the reconstructed surface area was 58% and 79% for the pre- and post-operative scan, respectively. For the bladder phantom the full surface was reconstructed and the mean reprojection error was 0.081 mm (range 0-0.79 mm). In inter-session comparison the changes in texture were correctly indicated for all six locations. CONCLUSION: The proposed proof of concept was able to perform 3-D and 2-D reconstruction of an in vivo bladder wall based on a set of monocular images. In a phantom study the computer vision algorithms were also effective in co-registering reconstructions of successive sessions and highlighting texture changes between sessions. These techniques may be useful for detecting, monitoring and revisiting suspicious lesions.

Ultrasound-guided breast biopsy using an adapted automated cone-based ultrasound scanner: a feasibility study.

BACKGROUND: Among available breast biopsy techniques, ultrasound (US)-guided biopsy is preferable because it is relatively inexpensive and provides live imaging feedback. The availability of magnetic resonance imaging (MRI)-3D US image fusion would facilitate US-guided biopsy even for US occult lesions to reduce the need for expensive and time-consuming MRI-guided biopsy. In this paper, we propose a novel Automated Cone-based Breast Ultrasound Scanning and Biopsy System (ACBUS-BS) to scan and biopsy breasts of women in prone position. It is based on a previously developed system, called ACBUS, that facilitates MRI-3D US image fusion imaging of the breast employing a conical container filled with coupling medium. PURPOSE: The purpose of this study was to introduce the ABCUS-BS system and demonstrate its feasibility for biopsy of US occult lesions. METHOD: The biopsy procedure with the ACBUS-BS comprises four steps: target localization, positioning, preparation, and biopsy. The biopsy outcome can be impacted by 5 types of errors: due to lesion segmentation, MRI-3D US registration, navigation, lesion tracking during repositioning, and US inaccuracy (due to sound speed difference between the sample and the one used for image reconstruction). For the quantification, we use a soft custom-made polyvinyl alcohol phantom (PVA) containing eight lesions (three US-occult and five US-visible lesions of 10 mm in diameter) and a commercial breast mimicking phantom with a median stiffness of 7.6 and 28 kPa, respectively. Errors of all types were quantified using the custom-made phantom. The error due to lesion tracking was also quantified with the commercial phantom. Finally, the technology was validated by biopsying the custom-made phantom and comparing the size of the biopsied material to the original lesion size. The average size of the 10-mm-sized lesions in the biopsy specimen was 7.00 ± 0.92 mm (6.33 ± 1.16 mm for US occult lesions, and 7.40 ± 0.55 mm for US-visible lesions). RESULTS: For the PVA phantom, the errors due to registration, navigation, lesion tracking during repositioning, and US inaccuracy were 1.33, 0.30, 2.12, and 0.55 mm. The total error was 4.01 mm. For the commercial phantom, the error due to lesion tracking was estimated at 1.10 mm, and the total error was 4.11 mm. Given these results, the system is expected to successfully biopsy lesions larger than 8.22 mm in diameter. Patient studies will have to be carried out to confirm this in vivo. CONCLUSION: The ACBUS-BS facilitates US-guided biopsy of lesions detected in pre-MRI and therefore might offer a low-cost alternative to MRI-guided biopsy. We demonstrated the feasibility of the approach by successfully taking biopsies of five US-visible and three US-occult lesions embedded in a soft breast-shaped phantom.

Quantitative Evaluation of an Automated Cone-Based Breast Ultrasound Scanner for MRI-3D US Image Fusion.

Breast cancer is one of the most diagnosed types of cancer worldwide. Volumetric ultrasound breast imaging, combined with MRI can improve lesion detection rate, reduce examination time, and improve lesion diagnosis. However, to our knowledge, there are no 3D US breast imaging systems available that facilitate 3D US - MRI image fusion. In this paper, a novel Automated Cone-based Breast Ultrasound System (ACBUS) is introduced. The system facilitates volumetric ultrasound acquisition of the breast in a prone position without deforming it by the US transducer. Quality of ACBUS images for reconstructions at different voxel sizes (0.25 and 0.50 mm isotropic) was compared to quality of the Automated Breast Volumetric Scanner (ABVS) (Siemens Ultrasound, Issaquah, WA, USA) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and resolution using a custom made phantom. The ACBUS image data were registered to MRI image data utilizing surface matching and the registration accuracy was quantified using an internal marker. The technology was also evaluated in vivo. The phantom-based quantitative analysis demonstrated that ACBUS can deliver volumetric breast images with an image quality similar to the images delivered by a currently commercially available Siemens ABVS. We demonstrate on the phantom and in vivo that ACBUS enables adequate MRI-3D US fusion. To our conclusion, ACBUS might be a suitable candidate for a second-look breast US exam, patient follow-up, and US guided biopsy planning.

Design of an end-effector for robot-assisted ultrasound-guided breast biopsies.

PURPOSE: The biopsy procedure is an important phase in breast cancer diagnosis. Accurate breast imaging and precise needle placement are crucial in lesion targeting. This paper presents an end-effector (EE) for robotic 3D ultrasound (US) breast acquisitions and US-guided breast biopsies. The EE mechanically guides the needle to a specified target within the US plane. The needle is controlled in all degrees of freedom (DOFs) except for the direction of insertion, which is controlled by the radiologist. It determines the correct needle depth and stops the needle accordingly. METHOD: In the envisioned procedure, a robotic arm performs localization of the breast, 3D US volume acquisition and reconstruction, target identification and needle guidance. Therefore, the EE is equipped with a stereo camera setup, a picobeamer, US probe holder, a three-DOF needle guide and a needle stop. The design was realized by prototyping techniques. Experiments were performed to determine needle placement accuracy in-air. The EE was placed on a seven-DOF robotic manipulator to determine the biopsy accuracy on a cuboid phantom. RESULTS: Needle placement accuracy was 0.3 ± 1.5 mm in and 0.1 ± 0.36 mm out of the US plane. Needle depth was regulated with an accuracy of 100 µm (maximum error 0.89 mm). The maximum holding force of the stop was approximately 6 N. The system reached a Euclidean distance error of 3.21 mm between the needle tip and the target and a normal distance of 3.03 mm between the needle trajectory and the target. CONCLUSION: An all in one solution was presented which, attached to a robotic arm, assists the radiologist in breast cancer imaging and biopsy. It has a high needle placement accuracy, yet the radiologist is in control like in the conventional procedure.

Production and clinical evaluation of breast lesion skin markers for automated three-dimensional ultrasonography of the breast: a pilot study.

OBJECTIVES: Automated ultrasound of the breast has the advantage to have the whole breast scanned by technicians. Consequently, feedback to the radiologist about concurrent focal abnormalities (e.g., palpable lesions) is lost. To enable marking of patient- or physician-reported focal abnormalities, we aimed to develop skin markers that can be used without disturbing the interpretability of the image. METHODS: Disk-shaped markers were casted out of silicone. In this IRB-approved prospective study, 16 patients were included with a mean age of 57 (39-85). In all patients, the same volume was imaged twice using an automated breast ultrasound system, once with and once without a marker in place. Nine radiologists from two medical centers filled scoring forms regarding image quality, image interpretation, and confidence in providing a diagnosis based on the images. RESULTS: Marker adhesion was sufficient for automated scanning. Observer scores showed a significant shift in scores from excellent to good regarding diagnostic yield/image quality (χ2, 15.99, p < 0.01), and image noise (χ2, 21.20, p < 0.01) due to marker presence. In 93% of cases, the median score of observers "agree" with the statement that marker-induced noise did not influence image interpretability. Marker presence did not interfere with confidence in diagnosis (χ2, 6.00, p = 0.20). CONCLUSION: Inexpensive, easy producible skin markers can be used for accurate lesion marking in automated ultrasound examinations of the breast while image interpretability is preserved. Any marker-induced noise and decreased image quality did not affect confidence in providing a diagnosis. KEY POINTS: • The use of a skin marker enables the reporting radiologist to identify a location which a patient is concerned about. • The developed skin marker can be used for accurate breast lesion marking in ultrasound examinations.

Analytical derivation of elasticity in breast phantoms for deformation tracking.

PURPOSE: Patient-specific biomedical modeling of the breast is of interest for medical applications such as image registration, image guided procedures and the alignment for biopsy or surgery purposes. The computation of elastic properties is essential to simulate deformations in a realistic way. This study presents an innovative analytical method to compute the elastic modulus and evaluate the elasticity of a breast using magnetic resonance (MRI) images of breast phantoms. METHODS: An analytical method for elasticity computation was developed and subsequently validated on a series of geometric shapes, and on four physical breast phantoms that are supported by a planar frame. This method can compute the elasticity of a shape directly from a set of MRI scans. For comparison, elasticity values were also computed numerically using two different simulation software packages. RESULTS: Application of the different methods on the geometric shapes shows that the analytically derived elongation differs from simulated elongation by less than 9% for cylindrical shapes, and up to 18% for other shapes that are also substantially vertically supported by a planar base. For the four physical breast phantoms, the analytically derived elasticity differs from numeric elasticity by 18% on average, which is in accordance with the difference in elongation estimation for the geometric shapes. The analytic method has shown to be multiple orders of magnitude faster than the numerical methods. CONCLUSION: It can be concluded that the analytical elasticity computation method has good potential to supplement or replace numerical elasticity simulations in gravity-induced deformations, for shapes that are substantially supported by a planar base perpendicular to the gravitational field. The error is manageable, while the calculation procedure takes less than one second as opposed to multiple minutes with numerical methods. The results will be used in the MRI and Ultrasound Robotic Assisted Biopsy (MURAB) project.

Stormram 4: An MR Safe Robotic System for Breast Biopsy.

Suspicious lesions in the breast that are only visible on magnetic resonance imaging (MRI) need to be biopsied under MR guidance with high accuracy and efficiency for accurate diagnosis. The aim of this study is to present a novel robotic system, the Stormram 4, and to perform preclinical tests in an MRI environment. Excluding racks and needle, its dimensions are 72 × 51 × 40 mm. The Stormram 4 is driven by two linear and two curved pneumatic stepper motors. The linear motor is capable of exerting 63 N of force at a pressure of 0.65 MPa. In an MRI environment the maximum observed stepping frequency is 30 Hz (unloaded), or 8 Hz when full force is needed. The Stormram 4's mean positioning error is 0.73 ± 0.47 mm in free air, and 1.29 ± 0.59 mm when targeting breast phantoms in MRI. Excluding the off-the-shelf needle, the robot is inherently MR safe. The robot is able to accurately target lesions under MRI guidance, reducing tissue damage and risk of false negatives. These results are promising for clinical experiments, improving the quality of healthcare in the field of MRI-guided breast biopsies.

Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies.

BACKGROUND: Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. METHODS: Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. RESULTS: The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. CONCLUSIONS: Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition.

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.

Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits.

Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). Understanding the neural mechanisms of this deficit is crucial for the development of efficient methods for treatment monitoring and augmentation of cognitive functions in PD patients. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson's Progression Marker Initiative (PPMI) database. Eighteen patients from this sample were also scanned with (123)I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs) defined from the AAL brain atlas. The Brain Connectivity Toolbox (BCT) was used to extract nodal strength from all ROIs, and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable (LV) scores were matched with the performances in the three cognitive domains (memory, visuospatial, and executive) and striatal dopamine transporter binding ratios (SBR) using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on the modularity of the "cognitive network" was analyzed. For the range of deficits studied, better executive performance was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This profile was also characterized by a relative preservation of nigrostriatal dopaminergic function. The profile associated with better memory performance correlated with increased prefronto-limbic processing, and was not associated with presynaptic striatal dopamine uptake. SBR ratios were negatively correlated with modularity of the "cognitive network," suggesting integrative effects of the preserved nigrostriatal dopamine system on this circuitry.

(123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study.

OBJECTIVES: Little is known regarding the 'false-negative' or 'false-positive' striatal dopamine transporter binding on SPECT for the diagnosis of dementia with Lewy bodies (DLB). We explored the clinical course in patients fulfilling the criteria for clinical DLB with a normal ((123)I)FP-CIT SPECT (ie, SPECT scan negative, clinical features positive (S-CF+)) and patients not fulfilling DLB criteria with an abnormal scan (S+CF-). DESIGN: Longitudinal case study over 2-5 years. SETTING: Consecutive referrals of patients with mild dementia to dementia clinics in western Norway. PARTICIPANTS: 50 patients (27 men and 23 women; mean age at baseline of 74 (range 52-88)) with ((123)I)FP-CIT SPECT images underwent cluster analysis: 20/50 patients allocated to a 'DLB' and 8 to a 'non-DLB' cluster were included. OUTCOME MEASURES: Scores on standardised clinical rating scales for hallucinations, parkinsonism, fluctuations, rapid eye movement (REM) sleep behaviour disorder and visually rated ((123)I)FP-CIT SPECT. RESULTS: During the follow-up period, in the S+CF- group (n=7), frequency and severity of DLB symptoms tended to increase, particularly parkinsonism (7/7) and cognitive fluctuations (7/7), while severity of visual hallucinations and REM sleep behaviour disorder remained stable. The S-CF+ (n=3) fulfilled the operationalised criteria for probable DLB both at baseline and at the end of the follow-up. CONCLUSIONS: The findings suggest that systematic visual analyses of ((123)I)FP-CIT SPECT can detect people with DLB prior to the development of the full clinical syndrome. In addition, the study indicates that some patients fulfilling clinical criteria for probable DLB have a normal scan, and further studies are required to characterise these patients better.

Validation of cephalic index measurements in scaphocephaly.

INTRODUCTION: The cephalic index (CI) of the head can be measured manually using a caliper, the original technique, but it is also possible to determine it using skull X-ray, 2DCT and 3DCT images, 3D photo and with help of plagiocephalometry (PCM). PATIENTS AND METHODS: In this study, the manual caliper determination is statistically compared with other measuring methods for scaphocephaly patients (n = 39). RESULTS: The CI mean differences for the most representative data are sequentially 3.74, 2.16, 1.09 and 0.97 for the 2DCT, PCM, 3D photo and 3DCT techniques. The CI 2DCT values show a significant difference (p < 0.01) in reference to CI manually, while the other techniques show a p > 0.05. CONCLUSION: The conclusions are that significantly different results are achieved when using 2DCT relative to the manual caliper determination. No significant difference is observed between the 3D techniques and the manual method.

Targeted lymph node biopsy in mediastinoscopy using 3D FDG-PET/CT movies: a feasibility study.

In non-small-cell lung cancer, positive lymph nodes with increased fluorodeoxyglucose (FDG) uptake may be missed by mediastinoscopy. Lack of pathological confirmation may lead to radical, but unnecessary lung surgery. To minimize these false-negative results, the feasibility and potential value of three-dimensional (3D) FDG-PET/computed tomography (CT) movies were investigated to improve targeted lymph node biopsy during mediastinoscopies. PET/CT images were rendered in 3D volumes with multiplanar reconstructions and maximum intensity projections and reviewed in 3D 'fly-through' and 'fly-around' movies. These movies were developed and optimized by the Departments of Surgery and Nuclear Medicine. Twenty-two consecutive patients with non-small-cell lung cancer were included, of whom eight were FDG-PET positive for mediastinal lymph nodes. 3D FDG-PET/CT movies were presented to surgeons before mediastinoscopy. Surgical consequences were investigated, including sensitivity and the negative predictive value of mediastinoscopy. Results were compared with those of a retrospective study in which 3D techniques were not used. During mediastinoscopies, the 3D-PET/CT movies were found to be helpful in the surgical localization of FDG-positive lymph nodes. It led to more confidence in the surgical approach. The sensitivity and negative predictive value were 86 and 94%, respectively. Although not statistically significant, these results were higher compared with those of the retrospective study (75 and 92%, respectively). 3D FDG-PET/CT guidance during mediastinoscopy is feasible. The movies seem to lead to targeted biopsy of lymph nodes. They may reduce false-negative mediastinoscopies and improve staging of lung cancer. 3D FDG-PET/CT can be seen as a promising tool for further implementation of image-guided surgery.

Early and presenting symptoms of dementia with lewy bodies.

BACKGROUND/AIMS: To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). METHOD: Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer's disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. RESULTS: Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. CONCLUSION: DLB should be suspected in predementia cases with visual hallucinations.