CBCT-based navigation system for open liver surgery: Accurate guidance toward mobile and deformable targets with a semi-rigid organ approximation and electromagnetic tracking of the liver.

Purpose: The surgical navigation system that provides guidance throughout the surgery can facilitate safer and more radical liver resections, but such a system should also be able to handle organ motion. This work investigates the accuracy of intraoperative surgical guidance during open liver resection, with a semi-rigid organ approximation and electromagnetic tracking of the target area.

Methods: The suggested navigation technique incorporates a preoperative 3D liver model based on diagnostic 4D MRI scan, intraoperative contrast-enhanced CBCT imaging and electromagnetic (EM) tracking of the liver surface, as well as surgical instruments, by means of six degrees-of-freedom micro-EM sensors.

A workflow for automated segmentation of the liver surface, hepatic vasculature and biliary tree anatomy from multiphase MR images.

Accurate assessment of 3D models of patient-specific anatomy of the liver, including underlying hepatic and biliary tree, is critical for preparation and safe execution of complex liver resections, especially due to high variability of biliary and hepatic artery anatomies. Dynamic MRI with hepatospecific contrast agents is currently the only type of diagnostic imaging that provides all anatomical information required for generation of such a model, yet there is no information in the literature on how the complete 3D model can be generated automatically. In this work, a new automated segmentation workflow for extraction of patient-specific 3D model of the liver, hepatovascular and biliary anatomy from a single multiphase MRI acquisition is developed and quantitatively evaluated.

Intraoperative verification of resection margins of maxillary malignancies by cone-beam computed tomography.

Resection of maxillary cancer often results in incomplete excision because of the tumour's proximity to important structures such as the orbit. To deal with this problem we prospectively investigated the feasibility of intraoperative imaging during maxillectomy to verify the planned resection margins. In total, six patients diagnosed with maxillary cancer listed for maxillectomy were included, irrespective of the histological type of tumour.

Prospective study on image-guided navigation surgery for pelvic malignancies.

Background And Objectives: Surgery of advanced tumors and lymph nodes in the pelvis can be challenging due to the narrow pelvic space and vital surrounding structures. This study explores the application of a novel electromagnetic navigation system to guide pelvic surgery.

Methods: This was a prospective study on surgery for malignancies in the pelvis.

Enrichment of high-grade tumors in breast cancer gene expression studies.

Purpose: Gene expression (GE) profiling for breast cancer classification and prognostication has become increasingly used in clinical diagnostics. GE profiling requires a reasonable tumor cell percentage and high-quality RNA. As a consequence, a certain amount of samples drop out.

Nutritional Supplement Use by Dutch Elite and Sub-Elite Athletes: Does Receiving Dietary Counseling Make a Difference?

The use of nutritional supplements is highly prevalent among athletes. In this cross-sectional study, we assessed the prevalence of nutritional supplement use by a large group of Dutch competitive athletes in relation to dietary counseling. A total of 778 athletes (407 males and 371 females) completed a web-based questionnaire about the use of nutritional supplements.

The hidden sentinel node in breast cancer: Reevaluating the role of SPECT/CT and tracer reinjection.

Introduction: Lymphoscintigraphy with planar imaging is considered a helpful tool to depict lymph node drainage in patients with invasive breast cancer. Single Photon Emission Computed Tomography with integrated CT (SPECT/CT) is usually performed to detect sentinel nodes (SN)s in breast cancer patients showing non-visualisation on lymphoscintigraphy. Incorporation of new SN indications (recurrent surgery, previous radiotherapy, or neo-adjuvant chemotherapy) has led to an increase of non-visualisation rates.

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

Background: Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe.

Fusion of Freehand SPECT and Ultrasound to Perform Ultrasound-Guided Fine-Needle Aspiration Cytology of Sentinel Nodes in Head and Neck Cancer.

Background And Purpose: Criteria for ultrasound-guided fine-needle aspiration cytology (USgFNAC) for the detection of occult lymph node metastasis in patients with clinically negative head and neck cancer are based on the morphology of cervical lymph nodes. To improve the selection of lymph nodes for USgFNAC, we examined the feasibility of fused freehand single-photon emission tomography ultrasound-guided fine-needle cytology (freehand SPECT-USgFNAC) of sentinel nodes in patients with early stage oral and head and neck skin cancer.

Materials And Methods: Six patients with early-stage head and neck cancer (4 oral and 2 head and neck skin cancers) and a clinically negative neck who were scheduled for transoral or local excision and a sentinel node procedure underwent USgFNAC and freehand SPECT-USgFNAC preoperatively.

Improved Accuracy and Reproducibility Using a Training Protocol for Freehand-SPECT 3D Mapping in Radio-Guided Surgery.

Purpose: Freehand single-photon emission computed tomography (SPECT) (fh-SPECT) for optical tracked 3-dimensional radioactivity mapping raises popularity for sentinel node biopsy and other radio-guided procedures. However, the device seems to be complex, requiring both training and a standardized scan protocol. Therefore, the aim of this study was to compare handling reproducibility between novice and expert users; subsequently, using additional scans, we evaluated a standardized scan protocol to be tested in novice users after receiving training.

Simultaneous use of an (125)I-seed to guide tumour excision and (99m)Tc-nanocolloid for sentinel node biopsy in non-palpable breast-conserving surgery.

Purpose: In the present study we describe patients with non-palpable breast lesions, in which an Iodine-125 ((125)I)-marker (or "seed") for excision of the primary tumour and Technetium-99m nanocolloid ((99m)Tc-nanocolloid) for sentinel node biopsy (SNB) are used simultaneously. The purpose was to investigate any interference between (125)I-seeds and (99m)Tc-nanocolloid by an in vitro and in vivo analysis.

Methods: Contrast/interference-ratios between (125)I and (99m)Tc count-rates were determined in vitro using a realistic simulation model.

Radio-guided seed localization for breast cancer excision: an ex-vivo specimen-based study to establish the accuracy of a freehand-SPECT device in predicting resection margins.

Purpose: Radioactive seed localization (RSL) uses an iodine-125 ((125)I) seed as a marker for tumour location. The (125)I seed is implanted into the tumour and enables intraoperative localization with a conventional gamma probe. However, specimen margins in relation to the (125)I seed are estimated on the basis of gamma-probe readings only.

Feasibility of preoperative (125)I seed-guided tumoural tracer injection using freehand SPECT for sentinel lymph node mapping in non-palpable breast cancer.

Background: This study was designed to explore the feasibility of replacing the conventional peri-/intratumoural ultrasound (US)-guided technetium-99m albumin nanocolloid ((99m)Tc-nanocolloid) administration by an injection of the same tracer guided by a freehand single-photon emission computed tomography (SPECT) device in patients with non-palpable breast cancer with an iodine-125 ((125)I) seed as tumour marker, who are scheduled for a sentinel lymph node biopsy (SLNB). This approach aimed to decrease the workload of the radiology department, avoiding a second US-guided procedure.

Methods: In ten patients, the implanted (125)I seed was primarily localised using freehand SPECT and subsequently verified by conventional US in order to inject the (99m)Tc-nanocolloid.

Chlorophenylpiperazine analogues as high affinity dopamine transporter ligands.

Selective σ2 ligands continue to be an active target for medications to attenuate the effects of psychostimulants. In the course of our studies to determine the optimal substituents in the σ2-selective phenyl piperazines analogues with reduced activity at other neurotransmitter systems, we discovered that 1-(3-chlorophenyl)-4-phenethylpiperazine actually had preferentially increased affinity for dopamine transporters (DAT), yielding a highly selective DAT ligand.

Trifluoromethoxyl substituted phenylethylene diamines as high affinity sigma receptor ligands with potent anti-cocaine actions.

The phenylethylene diamines are a class of sigma receptor ligands with excellent selectivity over other biological systems and with anti-cocaine actions that involve antagonism of sigma1 receptors. In order to increase the potency of the aromatic methoxyl substituted analogues, trifluoromethoxyl groups were introduced to prevent metabolic demethylation. The para-substituted trifluoromethoxyl substituted analogues were shown to have increased sigma receptor affinity and represent the most potent anti-cocaine phenylethylene diamines yet described.

Effects of UMB24 and (+/-)-SM 21, putative sigma2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice.

Earlier studies have demonstrated that antagonism of sigma1 receptors attenuates the convulsive, lethal, locomotor stimulatory and rewarding actions of cocaine in mice. In contrast, the contribution of sigma2 receptors is unclear because experimental tools to selectively target this subtype are unavailable. To begin addressing this need, we characterized UMB24 (1-(2-phenethyl)-4-(2-pyridyl)-piperazine) and (+/-)-SM 21 (3alpha-tropanyl-2-(4-chorophenoxy)butyrate) in receptor binding and behavioral studies.

Involvement of sigma (sigma) receptors in the acute actions of methamphetamine: receptor binding and behavioral studies.

Methamphetamine interacts with sigma (sigma) receptors, suggesting that the drug produces some of its physiological and behavioral effects through these sites. Therefore, in the present report, receptor binding and pharmacological studies were performed to characterize the interaction between methamphetamine and sigma receptors. Of the two major sigma receptor subtypes, sigma1 and sigma2, competition binding studies showed that methamphetamine has a 22-fold preferential affinity for the sigma1 subtype.

Novel analogs of the sigma receptor ligand BD1008 attenuate cocaine-induced toxicity in mice.

Previous studies have shown that BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) and related analogs attenuate the toxicity and stimulant effects of cocaine through antagonism of sigma receptors. In the present study, six analogs of BD1008 (UMB 98-103) were synthesized and evaluated in receptor binding and behavioral studies. Competition binding studies confirmed that all six compounds have high affinity for sigma1 receptors, moderate affinity for sigma2 receptors, and low to negligible affinity for monoamine transporters, opioid, N-methyl-D-aspartate, dopamine, and 5-HT receptors.

Structure-activity comparison of YZ-069, a novel sigma ligand, and four analogs in receptor binding and behavioral studies.

Earlier studies show that antagonism of sigma receptors using high to moderate affinity compounds or antisense oligodeoxynucleotides targeting the sigma(1) subtype significantly attenuates the behavioral effects of cocaine in mice. In this study, the novel sigma receptor ligand YZ-069 [N-phenylpropyl-N'-(3,4-dichlorophenethyl)piperazine] and four analogs (representing nitrophenyl and methoxyphenyl derivatives) were evaluated in receptor binding and behavioral studies to further delineate structural features that convey favorable anticocaine actions. In receptor binding studies, all of the compounds had low nanomolar affinities for sigma(1) and sigma(2) receptors but only micromolar affinities for monoamine transporters.

Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides.

Pharmacological and molecular biological tools were used to validate the involvement of sigma receptors in the actions of cocaine. Radioligand binding studies demonstrated significant levels of sigma receptors in the brain and heart, where cocaine interacts preferentially with the sigma(1) subtype. In behavioral pharmacological studies using mice, nine novel sigma receptor antagonists significantly attenuated cocaine-induced convulsions, while structural analogs with weak interactions with sigma receptors were ineffective.

Rimcazole analogs attenuate the convulsive effects of cocaine: correlation with binding to sigma receptors rather than dopamine transporters.

Cocaine interacts with dopamine transporters and sigma receptors at concentrations that are achievable in vivo, suggesting that they may both be viable targets for the development of anti-cocaine agents. Rimcazole binds to both of these targets and also attenuates cocaine-induced locomotor activity and sensitization. To further characterize the mechanism(s) underlying the attenuation of cocaine-induced convulsions and lethality, rimcazole and three analogs (SH3/24, SH2/21, SH1/57), with a range of affinities for dopamine transporters and sigma receptors, were evaluated.

Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.

Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.

N-alkyl substituted analogs of the sigma receptor ligand BD1008 and traditional sigma receptor ligands affect cocaine-induced convulsions and lethality in mice.

Cocaine binds to sigma receptors with comparable affinity to its well-established interaction with dopamine transporters. Previous studies have shown BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) to have high affinity and selectivity for sigma receptors, and to additionally attenuate the locomotor stimulatory effects of cocaine. Therefore, in the present study, three N-alkyl substituted analogs of BD1008 were characterized in receptor binding and behavioral studies: BD1060 (N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)ethylamine), BD1067 (N-[2-(3,4-dichlorophenyl)ethyl]-N-ethyl-2-(1-pyrrolidinyl)ethylamine), and BD1052 (N-[2-(3,4-dichlorophenyl)ethyl]-N-allyl-2-(1-pyrrolidinyl)ethylamine).

Correlation between neuroleptic binding to sigma(1) and sigma(2) receptors and acute dystonic reactions.

Acute dystonic reactions are motor side effects that occur soon after the initiation of neuroleptic treatment. Although earlier studies indicate that these abnormal movements can be induced in animals and humans via activation of sigma receptors, the relative contribution of the different sigma receptor subtypes is unknown. Since sigma(1) and sigma(2) receptor are differentially represented in motor regions of the brain, the affinities of 17 neuroleptics for these sigma receptor subtypes were determined using competition binding studies.