Rational approach to design gold nanoparticles for photothermal therapy: the effect of gold salt on physicochemical, optical and biological properties.

Among the unique characteristics associated to gold nanoparticles (AuNPs) in biomedicine, their ability to convert light energy into heat opens ventures for improved cancer therapeutic options, such as photothermal therapy (PTT). PTT relies on the local hyperthermia of tumor cells upon irradiation with light beams, and the association of AuNPs with radiation within the near infrared (NIR) range constitutes an advantageous strategy to potentially improve PTT efficacy. Herein, it was explored the effect of the gold salt on the AuNPs' physicochemical and optical properties. Mostly spherical-like negatively charged AuNPs with variable sizes and absorbance spectra were obtained. In addition, photothermal features were assessed using in vitro phantom models. The best formulation showed the ability to increase their temperature in aqueous solution up to 19 °C when irradiated with a NIR laser for 20 min. Moreover, scanning transmission electron microscopy confirmed the rearrangement of the gold atoms in a face-centered cubic structure, which further allowed to calculate the photothermal conversion efficiency upon combination of theoretical and experimental data. AuNPs also showed local retention after being locally administered in in vivo models. These last results obtained by computerized tomography allow to consider these AuNPs as promising elements for a PTT system. Moreover, AuNPs showed high potential for PTT by resulting in in vitro cancer cells' viability reductions superior to 70 % once combine with 5 min of NIR irradiation.

How the Number and Distance of Electrodes Change the Induced Electric Field in the Cortex during Multichannel tDCS.

Multichannel transcranial direct current stimulation (tDCS) is a promising approach to target neuromodulation of neural networks by making use of variable number of electrodes and distances to facilitate/inhibit specific connectivity patterns. Optimization of the electric field (EF) spatial distribution through computational models can provide a more accurate definition of the stimulation settings that are more effective. In this study, we investigate the effect of increasing the number of cathodes around a central anode placed over the target. We demonstrate that anode-cathode distance has the largest influence in the EF and using more than 3 cathodes did not result in considerable changes in the EF magnitude and direction. This could be relevant for simultaneous tDCS-electroencephalography (EEG) applications, by saving electrode positions for EEG acquisition. Clinical Relevance- This study demonstrates that distance between electrodes is more relevant than electrode number in determining the electric field distribution, and that a highly-focused stimulation can be equally effective with fewer electrodes.

Biological Thermal Performance of Organic and Inorganic Aerogels as Patches for Photothermal Therapy.

Aerogels are materials with unique properties, among which are low density and thermal conductivity. They are also known for their exquisite biocompatibility and biodegradability. All these features make them attractive for biomedical applications, such as their potential use in photothermal therapy (PTT). This technique is, yet, still associated with undesirable effects on surrounding tissues which emphasizes the need to minimize the exposure of healthy regions. One way to do so relies on the use of materials able to block the radiation and the heat generated. Aerogels might be potentially useful for this purpose by acting as insulators. Silica- and pectin-based aerogels are reported as the best inorganic and organic thermal insulators, respectively; thus, the aim of this work relies on assessing the possibility of using these materials as light and thermal insulators and delimiters for PTT. Silica- and pectin-based aerogels were prepared and fully characterized. The thermal protection efficacy of the aerogels when irradiated with a near-infrared laser was assessed using phantoms and ex vivo grafts. Lastly, safety was assessed in human volunteers. Both types presented good textural properties and safe profiles. Moreover, thermal activation unveils the better performance of silica-based aerogels, confirming the potential of this material for PTT.

Nanogold-based materials in medicine: from their origins to their future.

The properties of gold-based materials have been explored for centuries in several research fields, including medicine. Multiple published production methods for gold nanoparticles (AuNPs) have shown that the physicochemical and optical properties of AuNPs depend on the production method used. These different AuNP properties have allowed exploration of their usefulness in countless distinct biomedical applications over the last few years. Here we present an extensive overview of the most commonly used AuNP production methods, the resulting distinct properties of the AuNPs and the potential application of these AuNPs in diagnostic and therapeutic approaches in biomedicine.

Impact of Navigated Task-specific fMRI on Direct Cortical Stimulation.

BACKGROUND AND STUDY AIMS: Cortical mapping (CM) with direct cortical stimulation (DCS) in awake craniotomy is used to preserve cognitive functions such as language. Nevertheless, patient collaboration during this procedure is influenced by previous neurological symptoms and growing discomfort with DCS duration. Our study aimed to evaluate the impact of navigated task-specific functional magnetic resonance imaging (nfMRI) on the practical aspects of DCS. MATERIAL AND METHODS: We recruited glioma patients scheduled for awake craniotomy for prior fMRI-based CM, acquired during motor and language tasks (i.e., verb generation, semantic and syntactic decision tasks). Language data was combined to generate a probabilistic map indicating brain regions activated with more than one paradigm. Presurgical neurophysiological language tests (i.e., verb generation, picture naming, and semantic tasks) were also performed. We considered for subsequent study only the patients with a minimum rate of correct responses of 50% in all tests. These patients were then randomized to perform intraoperative language CM either using the multimodal approach (mCM), using nfMRI and DCS combined, or electrical CM (eCM), with DCS alone. DCS was done while the patient performed picture naming and nonverbal semantic decision tasks. Methodological features such as DCS duration, number of stimuli, total delivered stimulus duration per task, and frequency of seizures were analyzed and compared between groups. The correspondence between positive responses obtained with DCS and nfMRI was also evaluated. RESULTS: Twenty-one surgeries were included, thirteen of which using mCM (i.e., test group). Patients with lower presurgical neuropsychological performance (correct response rate between 50 and 80% in language tests) showed a decreased DCS duration in comparison with the control group. None of the compared methodological features showed differences between groups. Correspondence between DCS and nfMRI was 100/84% in the identification of the precentral gyrus for motor function/opercular frontal inferior gyrus for language function, respectively. CONCLUSION: Navigated fMRI data did not influence DCS in practice. Presurgical language disturbances limited the applicability of DCS mapping in awake surgery.

Optimal b-values for diffusion kurtosis imaging in invasive ductal carcinoma versus ductal carcinoma in situ breast lesions.

Diffusion kurtosis imaging (DKI) is a diffusion-weighted MRI technique that probes the non-Gaussian diffusion of water molecules within biological tissues. The purpose of this study was to investigate the DKI model optimal b-values combinations in invasive ductal carcinoma (IDC) versus ductal carcinoma in situ (DCIS) breast lesions. The study included 114 malignant breast lesions (64 IDC and 50 DCIS). Patients underwent a breast MRI examination which included a diffusion-weighted sequence (b = 0-3000 s/mm2). For each lesion, the b-values were combined among each other (109 combinations) and each mean kurtosis (MK) parameter was obtained. Differences between the lesion groups and b-values combinations were assessed. Also, the diagnostic performance of the combinations was determined through receiver operating characteristic (ROC) curve analysis, and compared. Root mean square error (RMSE) was also obtained. All the b-values combinations showed significant differences between the lesion groups (p < 0.05). The combination 0, 50, 200, 750, 1000, 2000 s/mm2 showed the best performance (AUC = 0.930, sensitivity = 95.3%, specificity = 82.0%, accuracy = 89.5%), with a RMSE of 17.65. The b-values combinations with the worst performance were composed of only high or ultra-high b-values, or with b = 1000 s/mm2 as the maximum b-value. Better results were obtained when zero b-value was included in the DKI model fitting with at least one b-value below 1000 s/mm2 and one b-value above 1000 s/mm2 (conserving b = 1000 s/mm2). Six was the optimal number of b-values, nonetheless other combinations with less b-values may be considered, but with a consequent diagnostic performance loss.

Gamma Distribution Model in the Evaluation of Breast Cancer Through Diffusion-Weighted MRI: A Preliminary Study.

BACKGROUND: The gamma distribution (GD) model is based on the statistical distribution of the apparent diffusion coefficient (ADC) parameter. The GD model is expected to reflect the probability of the distribution of water molecule mobility in different regions of tissue, but also the intra- and extracellular diffusion and perfusion components (f1 , f2 , f3 fractions). PURPOSE: To assess the GD model in the characterization and diagnostic performance of breast lesions. STUDY TYPE: Prospective. POPULATION: In all, 48 females with 24 benign and 33 malignant breast lesions. FIELD STRENGTH/SEQUENCE: A diffusion-weighted sequence (b = 0-3000 s/mm2 ) with a 3 T scanner. ASSESSMENT: For each group of benign, malignant, invasive, and in situ breast lesions, the ADC was obtained. Also, θ and k parameters (scale and shape of the statistic distribution, respectively), f1 , f2 , and f3 fractions were obtained from fitting the GD model to diffusion data. STATISTICAL TESTS: Lesion types were compared regarding diffusion parameters using nonparametric statistics and receiver operating characteristic curve diagnostic performance. RESULTS: The majority of GD parameters (k, f1 , f2 , f3 fractions) showed significant differences between benign and malignant lesions, and between in situ and invasive lesions (f1 , f2 , f3 fractions) (P ≤ 0.001). The best diagnostic performances were obtained with ADC and f1 fraction in benign vs. malignant lesions (area under curve [AUC] = 0.923 and 0.913, sensitivity = 93.9% and 81.8%, specificity = 79.2% and 91.7%, accuracy = 87.7% and 86.0%, respectively). In invasive lesions vs. in situ lesions, the best diagnostic performance was obtained with f1 fraction, which outperformed ADC results (AUC = 0.978 and 0.941, and sensitivity = 91.3% for both parameters, specificity = 100.0% and 90.0%, accuracy = 93.9% and 90.9%, respectively). DATA CONCLUSION: This work shows that the GD model provides information in addition to the ADC parameter, suggesting its potential in the diagnosis of breast lesions. Level of Evidence 2: Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2019;50:230-238.

The Venoarteriolar Reflex Significantly Reduces Contralateral Perfusion as Part of the Lower Limb Circulatory Homeostasis in vivo.

Perfusion at microvascular level involves the contribution of both local and central regulators, under a complex vascular signaling frame. The venoarteriolar reflex (VAR) is one of such regulatory responses, of particular relevance in the lower limb to prevent edema. Although known for quite some time, many of the complex interactions involving all of these regulatory mechanisms still need clarification. Our objective was to look deeper into VAR through modern photoplethymography (PPG). Twelve healthy subjects (both sexes, 26.0 ± 5.0 y.o.) were enrolled in this study after informed written consent. Subjects were submitted to a leg lowering maneuver while lying supine to evoke the VAR, involving three phases-10 min baseline register, both legs extended, 10 min challenge, with one randomly chosen leg (test) pending 50 cm below heart level, while the contralateral (control) remained in place, and 10 minutes recovery, resuming the initial position. PPG signals were collected from both feet and treated by the wavelet transform (WT) revealing six spectral bands in frequency intervals comprising the cardiac [1.6-0.7 Hz], respiratory [0.4-0.26 Hz], myogenic [0.26-0.1 Hz], neurogenic/sympathetic [0.1-0.045 Hz], endothelial NO-dependent (NOd) [0.045-0.015 Hz], and NO-independent (NOi) [0.015-0.007 Hz] activities. For the first time, this approach revealed that, with VAR, perfusion significantly decreased in both limbs, although the change was more pronounced in the test foot. Here, a significant decrease in myogenic, neurogenic and NOd, were noted, while the control foot recorded a decrease in neurogenic and an increase in NOd. These results confirm the utility of WT spectral analysis for flowmotion. Further, it strongly suggests that VAR results from a complex cooperation between local myogenic-endothelial responses, where a central neurogenic reflex might also be involved.

Reconstruction of white matter fibre tracts using diffusion kurtosis tensor imaging at 1.5T: Pre-surgical planning in patients with gliomas.

Tractography studies for pre-surgical planning of primary brain tumors is typically done using diffusion tensor imaging (DTI), which cannot resolve crossing, kissing or highly angulated fibres. Tractography based on the estimation of the diffusion kurtosis (DK) tensor was recently demonstrated to enable tackling these limitations. However, its use in the clinical context at low 1.5T field has not yet been reported. PURPOSE: To evaluate if the estimation of whole-brain tractography using the DK tensor is feasible for pre-surgical investigation of patients with brain tumors at 1.5T. METHODS: Eight healthy subjects and 3 patients with brain tumors were scanned at 1.5T using a 12-channel head coil. Diffusion-weighted images were acquired with repetition/echo times of 5800/107 ms, 82 × 82 resolution, 3 × 3 × 3 mm3 voxel size, b-values of 0, 1000, 2000 s/mm2 and 64 gradient sensitising directions. Whole-brain tractography was estimated using the DK tensor and corticospinal tracts (CST) were isolated using regions-of-interest placed at the cerebral peduncles and motor gyrus. Tract size, DK metrics and CST deviation index (highest curvature point) were compared between healthy subjects and patients. RESULTS: Tract sizes did not differ between groups. The CST deviation index was significantly higher in patients compared to healthy subjects. Fractional anisotropy was significantly lower in patients, with higher mean kurtosis asymmetry index at the highest curvature point in patients. CONCLUSIONS: Corticospinal fibre bundles estimated using DK tensor in a 1.5T scanner presented similar properties in patients with brain gliomas as those reported in the literature using DTI-based tractography.

Motor preparation in picture naming tasks.

In certain circumstances, words can be uttered as an involuntary action. We hypothesize that, once pronunciation of a word is fully prepared it can be triggered as a reflex with no need for cortical processing. We used modified protocols of picture naming tasks, with different levels of cognitive demands, to measure reaction time to word pronunciation (RTWP). In test trials, picture presentation was accompanied by a startling auditory stimulus (SAS). When one and the same picture was repeatedly shown, SAS shortened RTWP by about 30% (StartReact effect), which did not occur when random pictures were shown. If subjects were led to learn which picture was to appear after repeated presentation of three pictures in sequence, they exhibited again the StartReact effect. We conclude that word pronunciation may be fully prepared for execution in absence of cognitive demands. However, the StartReact effect is inhibited during cognitive tasks.

Effects of prefrontal anodal transcranial direct current stimulation on working-memory and reaction time.

Transcranial direct current stimulation (tDCS) has proven to be a useful tool in the scientific research community, particularly for clinical investigation purposes. Neuroimaging studies indicate that there is a connection between the prefrontal cortex (PFC) and working memory (WM), as well as between the primary motor cortex and reaction time (RT). Thus, our goal was to evaluate the effect of anodal stimulation of the PFC, with respect to WM and RT. We tested 20 healthy subjects randomized into two groups - half received active stimulation and the other half sham stimulation. Participants underwent two stimulation sessions of 10 minutes each, separated by a 10-minute interval for rest. The task was performed during the stimulation periods, and consisted in the display of a list of words for the subject to read and memorize. Afterwards, a new list was shown and the subject was asked to to press a key when a repeated word appeared. A current of 1 mA was delivered via a foc.us gamer headset. After both stimulations, the participants answered an Adverse Effects Questionnaire. Statistical tests were performed to compare the accuracy, error rate, and reaction time values for active vs. sham and first vs. second stimulations. The results obtained led us to infer that there were no significant improvements in the performance of the active group in comparison with the sham group, in terms of WM and overall RT values. However, RT data analysis indicated that active simulation subjects showed significantly lower values when compared to the sham group, only for the first stimulation period. Due to emerging technological advances, the videogame industry has started to invest in the commercialization of products that promise to enhance neural functions and, thus, improve gamers' performance. The results obtained provide evidence of the importance of testing such commercial devices. The scientific community should have an active role in the validation of these claims.

Magnetoresistive-based biosensors and biochips.

Over the past five years, magnetoelectronics has emerged as a promising new platform technology for biosensor and biochip development. The techniques are based on the detection of the magnetic fringe field of a magnetically labeled biomolecule interacting with a complementary biomolecule bound to a magnetic-field sensor. Magnetoresistive-based sensors, conventionally used as read heads in hard disk drives, have been used in combination with biologically functionalized magnetic labels to demonstrate the detection of molecular recognition. Real-world bio-applications are now being investigated, enabling tailored device design, based on sensor and label characteristics. This detection platform provides a robust, inexpensive sensing technique with high sensitivity and considerable scope for quantitative signal data, enabling magnetoresistive biochips to meet specific diagnostic needs that are not met by existing technologies.