Nueva generación de radiotrazadores para la biopsia del ganglio centinela: ¿qué es necesario para establecer nuevos paradigmas de imagen?

Publication date: Available online 5 November 2018

Source: Revista Española de Medicina Nuclear e Imagen Molecular

Author(s): S. Vidal-Sicart, D.R. Vera, R.A. Valdés Olmos

Resumen

La biopsia del ganglio centinela (GC) es, en la actualidad, la técnica estándar para la estadificación regional de diversos tumores sólidos. La administración intersticial de un radiotrazador alrededor del tumor primario proporciona la posibilidad de obtener imágenes secuenciales con una gammacámara y visualizar el mapa linfático y los GC. Existe, sin embargo, una amplia variabilidad geográfica en estos radiotrazadores y, de este modo, los nanocoloides se utilizan mayoritariamente en Europa (con un intervalo de tamaño de partícula entre 15-100 nm), mientras que en Estados Unidos utiliza ampliamente el azufre coloidal (filtrado o no) marcado con ^99mTc (rango 20-1.000 nm). El nuevo radiotrazador ^99mTc-Tilmanocept, diseñado específicamente para la identificación de los GC, y recientemente introducido comercialmente en Estados Unidos y en Europa, parece tener la potencia para solucionar los inconvenientes descritos para los radiotrazadores convencionales utilizados hasta la fecha, transformando al mismo tiempo los paradigmas actuales de la imagen gammagráfica.

Tras definir los retos para la nueva generación de radiotrazadores, este artículo describe las propiedades del ^99mTc-Tilmanocept, su proceso de validación para la biopsia del GC y sus aplicaciones clínicas emergentes en diversas neoplasias malignas.

Abstract

Sentinel lymph node (SLN) biopsy is now the standard of care for regional staging in several solid tumors. The interstitial administration of a radiotracer around the primary tumor provide the possibility to sequentially obtain images with a gamma camera and visualize lymphatic mapping and the SLN. There is, however, a large geographical variability in those radiotracers and nanocolloids ranging from 15-100 nm are most widely employed in Europe, while filtered and unfiltered ^99mTc-sulfur colloid (range 20-1000 nm) is usually used in the USA with different drawbacks in its use. The new radiotracer ^99mTc-Tilmanocept, designed specifically for the identification of SLNs and recently becoming commercially available in USA and Europe, appears to have the potency to overcome the shortcomings described for the conventional radiotracers used until now for SLN biopsy and at the same time to transform current imaging paradigms.

After delineating the challenges for the next generation of radiotracers, this paper discusses the properties of ^99mTc-Tilmanocept, its validation process for SLN biopsy and its emerging clinical applications in various malignancies.

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Decentralized temporal independent component analysis: Leveraging fMRI data in collaborative settings

Publication date: Available online 5 November 2018

Source: NeuroImage

Author(s): Bradley T. Baker, Anees Abrol, Rogers F. Silva, Eswar Damaraju, Anand D. Sarwate, Vince D. Calhoun, Sergey M. Plis

Abstract

The field of neuroimaging has recently witnessed a strong shift towards data sharing; however, current collaborative research projects may be unable to leverage institutional architectures that collect and store data in local, centralized data centers. Additionally, though research groups are willing to grant access for collaborations, they often wish to maintain control of their data locally. These concerns may stem from research culture as well as privacy and accountability concerns. In order to leverage the potential of these aggregated larger data sets, we require tools that perform joint analyses without transmitting the data. Ideally, these tools would have similar performance and ease of use as their current centralized counterparts. In this paper, we propose and evaluate a new Algorithm, decentralized joint independent component analysis (djICA), which meets these technical requirements. djICA shares only intermediate statistics about the data, plausibly retaining privacy of the raw information to local sites, thus making it amenable to further privacy protections, for example via differential privacy. We validate our method on real functional magnetic resonance imaging (fMRI) data and show that it enables collaborative large-scale temporal ICA of fMRI, a rich vein of analysis as of yet largely unexplored, and which can benefit from the larger-N studies enabled by a decentralized approach. We show that djICA is robust to different distributions of data over sites, and that the temporal components estimated with djICA show activations similar to the temporal functional modes analyzed in previous work, thus solidifying djICA as a new, decentralized method oriented toward the frontiers of temporal independent component analysis.

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Volitional limbic neuromodulation has a multifaceted clinical benefit in Fibromyalgia patients

Publication date: Available online 5 November 2018

Source: NeuroImage

Author(s): Noam Goldway, Jacob Ablin, Omer Lubin, Yoav Zamir, Jackob Nimrod Keynan, Ayelet Or-Borichev, Marc Cavazza, Fred Charles, Nathan Intrator, Silviu Brill, Eti Ben-Simon, Haggai Sharon, Talma Hendler

Abstract

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplification effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation.

We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation should improve chronic pain in patients suffering from Fibromyalgia, by balancing disturbed indices for sleep and affect. We further expected that improved clinical status would correspond to successful training as indicated by improved down modulation of the Amygdala-EFP signal.

Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions and placebo of sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the Real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep Indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion.

REM latency and objective sleep quality index were robustly improved following the treatment course only in the Real-neurofeedback group (both time × group p < 0.05) and to a greater extent among good modulators (both time*sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the treatment. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the Real-neurofeedback group (both time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures.

Our findings suggest that Amyg-EFP- neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation training in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the necessary link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.

Graphical abstract

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Medical Ultrasound Disinfection and Hygiene Practices: WFUMB Global Survey Results

Publication date: Available online 6 November 2018

Source: Ultrasound in Medicine & Biology

Author(s): Susan Campbell Westerway, Jocelyne M. Basseal, Jacques S. Abramowicz

Abstract

As ultrasound technology rapidly evolves and is used more frequently in every area of medical diagnosis and treatment, it may be overlooked as a potential vector in the transmission of a health care-associated infection. A survey on disinfection and hygiene practice in medical ultrasound was disseminated via the World Federation for Ultrasound in Medicine and Biology (WFUMB) to its six member federations and associated ultrasound societies globally. One thousand twenty-nine responses were obtained across a broad range of ultrasound practitioners. A total of 76% of respondents used transducer covers every time to scan open wounds and 71% when blood and bodily fluids were present or for an interventional procedure. Approved high-level disinfectants are not always used, even when blood comes into contact with the transducer or after endocavity scans. Alcohol-based wipes were used by many respondents to clean both external transducers and endocavity transducers. Open-ended responses indicated that a large caseload hindered the time required for cleaning and that access to clear guidelines would be beneficial. Global survey results indicate that some users do not comply with disinfection practice, and there is a gap in knowledge on basic infection prevention and control education within the ultrasound unit. As the infectious status of a patient is not often disclosed prior to an ultrasound examination, training in suitable protocols for the cleaning and disinfection of ultrasound equipment is imperative to mitigate the risk of potential infection.

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Primary Application of Micro-Flow Imaging Technology in the Diagnosis of Hepatic Tumors

Publication date: Available online 5 November 2018

Source: Ultrasound in Medicine & Biology

Author(s): Hong Han, Hong Ding, Zhengbiao Ji, Weibin Zhang, Qun Wang, Wenping Wang

Abstract

The purpose of the study was to evaluate the vascular architecture of focal liver lesions with the newly released non-contrast micro-flow imaging (MFI) technique. Eighty patients with 80 hepatic tumors were enrolled in this study. The richness of displayed blood flow was first compared with color Doppler flow imaging using grades according to Adler's method. The results indicated that MFI outperformed color Doppler flow imaging with a statistically significant difference (p <0.0001). With the enhanced position in arterial phase of contrast-enhanced ultrasound imaging as the ground truth, the displayed blood flow distribution within tumors in MFI was further evaluated. The coincidence rate between MFI and contrast-enhanced ultrasound was 73.75% (59/80), which was higher than that of color Doppler flow imaging (52.5%, 42/80) (p < 0.0001). Moreover, for the five cases of focal nodular hyperplasia, MFI clearly revealed the spoke-wheel or radiating intra-tumoral vasculature, a finding specific to the diagnosis of focal nodular hyperplasia.

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Histological and inflammatory analysis to diagnostic method of proximal gingivitis by flossing

Abstract

Objectives

The aim of this study was to assess with histological and inflammatory analysis the use of flossing as a diagnostic method for detecting proximal gingivitis.

Material and methods

This is a diagnostic accuracy paper composed of two different studies. In the first study, three groups were identified based on papilla status: bleeding (+) with both methods (N = 26); bleeding (+) with dental floss, but no bleeding (−) with probing (N = 26); and no bleeding (−) with either method (N = 26). One papilla from all 78 participants was biopsied and analyzed for the determination of inflammatory infiltrate and percentage of collagen fibers. Sensibility, specificity, positive and negative predictive, and accuracy values were analyzed. In the second study, the volume of gingival crevicular fluid (GCF) was analyzed in 49 participants with flossing+/probing− and flossing−/probing− at contralateral proximal sites. The GCF volume was compared between these sites (n = 172).

Results

Significantly greater frequencies of moderate/intense inflammation were found in the flossing+/probing+ (100%) and flossing+/probing− (92.3%) groups compared to those in the flossing−/probing− (0%) group. Significantly different percentages of collagen fibers were found among the three groups (flossing+/probing+ (40.90 ± 3.68); flossing+/probing− (45.78 ± 4.55); flossing−/probing− (60.01 ± 36.66)) (P < 0.001). Dental floss increased the balance between sensitivity and specificity values and showed highest positive predictive (100%) and accuracy (97%) values. Among the 172 sites evaluated, positive bleeding sites had a significantly greater volume of GCF (38 (27–68)) than negative sites (25 (16–51)) (P < 0.001).

Conclusions

The findings suggest that flossing can be used as a diagnostic method for proximal gingivitis in subjects with no history of periodontitis.

Clinical relevance

Dental floss can be used as a complementary diagnostic method for proximal gingivitis in adults without clinical attachment loss in clinical practice as well as epidemiology studies.

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Cerebral oxygen metabolism during and after therapeutic hypothermia in neonatal hypoxic–ischemic encephalopathy: a feasibility study using magnetic resonance imaging

Abstract

Background

Therapeutic hypothermia is the standard-of-care treatment for infants diagnosed with moderate-to-severe hypoxic–ischemic encephalopathy (HIE). MRI for assessing brain injury is usually performed after hypothermia because of logistical challenges in bringing acutely sick infants receiving hypothermia from the neonatal intensive care unit (NICU) to the MRI suite. Perhaps examining and comparing early cerebral oxygen metabolism disturbances to those after rewarming will lead to a better understanding of the mechanisms of brain injury in HIE and the effects of therapeutic hypothermia.

Objective

The objectives were to assess the feasibility of performing a novel T2-relaxation under spin tagging (TRUST) MRI technique to measure venous oxygen saturation very early in the time course of treatment, 18–24 h after the initiation of therapeutic hypothermia, to provide a framework to measure neonatal cerebral oxygen metabolism noninvasively, and to compare parameters between early and post-hypothermia MRIs.

Materials and methods

Early (18–24 h after initiating hypothermia) MRIs were performed during hypothermia treatment in nine infants with HIE (six with moderate and three with severe HIE). Six infants subsequently had an MRI after hypothermia. Mean values of cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen from MRIs during hypothermia were compared between infants with moderate and severe HIE; and in those with moderate HIE, we compared cerebral oxygen metabolism parameters between MRIs performed during and after hypothermia.

Results

During the initial hypothermia MRI at 23.5±5.2 h after birth, infants with severe HIE had lower oxygen extraction fraction (P=0.04) and cerebral metabolic rate of oxygen (P=0.03) and a trend toward lower cerebral blood flow (P=0.33) compared to infants with moderate HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between MRIs during and after hypothermia (although not significantly); cerebral metabolic rate of oxygen (P=0.93) was not different.

Conclusion

Early MRIs were technically feasible while maintaining hypothermic goal temperatures in infants with HIE. Cerebral oxygen metabolism early during hypothermia is more disturbed in severe HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between early and post-hypothermia scans. A comparison of cerebral oxygen metabolism parameters between early and post-hypothermia MRIs might improve our understanding of the evolution of HIE and the benefits of hypothermia. This approach could guide the use of adjunctive neuroprotective strategies in affected infants.

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