Noninvasive virtual biopsy using micro-registered optical coherence tomography (OCT) in human subjects.

Histological hematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumor margin detection, and disease diagnosis. Producing H&E sections, however, is invasive and time-consuming. While deep learning has shown promise in virtual staining of unstained tissue slides, true virtual biopsy requires staining of images taken from intact tissue. In this work, we developed a micron-accuracy coregistration method [micro-registered optical coherence tomography (OCT)] that can take a two-dimensional (2D) H&E slide and find the exact corresponding section in a 3D OCT image taken from the original fresh tissue. We trained a conditional generative adversarial network using the paired dataset and showed high-fidelity conversion of noninvasive OCT images to virtually stained H&E slices in both 2D and 3D. Applying these trained neural networks to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.

Novas Pontes na Escuta: Laços e Territórios Virtuais no Cuidado dos Migrantes e Refugiados / New Device of Therapeutic Listening: Virtual Bonds and Territories in the Care of Migrants / Nuevos Puentes en la Escucha: Vínculos y Territorios Virtuales en la Atención a Migrantes

experiência do Projeto Ponte no atendimento de grupos terapêuticos online mostra a potência deste dispositivo no atendimento aos migrantes; nosso projeto defronte à pandemia teve de se adaptar a novos parâmetros no atendimento virtual. Participamos de uma rede de serviços específica ao público migrante, essencial na pandemia de COVID-19, para o apoio e continuidade do trabalho. As referências do projeto são: o conceito de interculturalidade, o atendimento grupal no formato slow open, a língua portuguesa e a psicanálise de grupos e vínculos. Nos atendimentos clínicos com migrantes, consideramos os processos de ruptura da migração, a dupla pertença aos países de origem e destino, bem como a dificuldade de se instalar no país de destino, a estranheza da experiência e o lugar de estrangeiro que o migrante ocupa. Por isso adotamos o dispositivo grupal, onde o migrante encontra um lugar para a construção e elaboração da migração, bem como para estabelecer uma possível pertença.

The experience of Ponte Project in attending therapeutic groups online shows the power that this device provokes in attending migrants; this work with the arrival of the COVID-19 pandemic had to adapt to the new parameters of virtual therapy. We also participate in a network in the psychological consultation of the migrant public, essential for the continuity of the project's work. The theoretical framework of the project has always been based on: the concept of interculturality, a slow-open group, Portuguese language and Psychoanalysis with groups and bonds. In clinical sessions with the migrants we will consider the processes of rupture caused by migration, the double belonging, as well as the difficulty of settling in the country of destination, all the strangeness caused by this experience and also the place of foreigner that the migrant occupies. That is why we chose to work with groups, where the migrant finds a place to elaborate the effects of migration, in addition to establishing a possible place of belonging.

La experiencia del Proyecto Puente en la atención terapéutica grupal en línea muestra la potencia de este dispositivo en la atención a migrantes. Nuestro proyecto, frente a la pandemia, tuvo que adaptarse a los nuevos parámetros para la atención virtual. Participamos en una red de servicios específicos para el público migrante, esencial en la pandemia del COVID-19, para brindar apoyo y continuidad al trabajo. Las referencias del proyecto son: el concepto de interculturalidad, la atención grupal en el formato slow open, la lengua portuguesa, el psicoanálisis de grupo y los vínculos. En las sesiones clínicas con migrantes consideramos los procesos de ruptura de la migración, la doble pertenencia a los países de origen y destino, la dificultad de integración en el país de destino, la extrañeza de la experiencia y el lugar de extranjero que ocupa el migrante. Por eso adoptamos el dispositivo grupal, donde el migrante encuentra un lugar para la construcción y elaboración de la experiencia migratoria, permitiéndole así establecer una posible pertenencia.

A Dense Conformal Electrode Array for High Spatial Resolution Stimulation of Electrosensory Systems.

Studies of electrosensory systems have led to insights into to a number of general issues in biology. However, investigations of these systems have been limited by the inability to precisely control spatial patterns of electrosensory input. In this paper, an electrode array and a system to selectively stimulate spatially restricted regions of an electroreceptor array is presented. The array has 96 channels consisting of chrome/gold electrodes patterned on a flexible parylene-C substrate and encapsulated with another parylene-C layer. The conformability of the electrode array allows for optimal current driving and surface interface conditions. Recordings of neural activity at the first central processing stage in weakly electric mormyrid fish support the potential of this system for high spatial resolution stimulation and mapping of electrosensory systems.

Elevated Intraocular Pressure in Periorbital Sweet's Syndrome.

A 66-year-old immunocompromised man presented with cellulitis around the left eye that was initially concerning for necrotizing fasciitis. Exam findings were remarkable for exquisite periocular tenderness with rigid, immobile eyelids resulting from severe erythema, edema, and induration. Given the concern for orbital compartment syndrome and a necrotizing infection, the patient was taken urgently to the operating room for debridement of the eyelid skin as well as an urgent lateral canthotomy and cantholysis. His eye exam revealed 360° of hemorrhagic chemosis, no relative afferent pupillary defect, and an ipsilateral elevated intraocular pressure of 35 mm Hg. No visual acuity measurement could be obtained secondary to the patient's altered mental status. His intraocular pressure normalized after treatment with antihypertensive drops and further extension of the canthotomy. Histopathological analysis showed extensive neutrophilic infiltrate of the dermis which was compatible with a diagnosis of Sweet's syndrome.

Intravital 3D visualization and segmentation of murine neural networks at micron resolution.

Optical coherence tomography (OCT) allows label-free, micron-scale 3D imaging of biological tissues' fine structures with significant depth and large field-of-view. Here we introduce a novel OCT-based neuroimaging setting, accompanied by a feature segmentation algorithm, which enables rapid, accurate, and high-resolution in vivo imaging of 700 µm depth across the mouse cortex. Using a commercial OCT device, we demonstrate 3D reconstruction of microarchitectural elements through a cortical column. Our system is sensitive to structural and cellular changes at micron-scale resolution in vivo, such as those from injury or disease. Therefore, it can serve as a tool to visualize and quantify spatiotemporal brain elasticity patterns. This highly transformative and versatile platform allows accurate investigation of brain cellular architectural changes by quantifying features such as brain cell bodies' density, volume, and average distance to the nearest cell. Hence, it may assist in longitudinal studies of microstructural tissue alteration in aging, injury, or disease in a living rodent brain.

Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management.

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.

Audiology findings in patients with teprotumumab associated otologic symptoms.

PURPOSE: To report a case series of subjective and objective hearing function changes associated with teprotumumab treatment for thyroid eye disease. OBSERVATIONS: A 74-year-old female with a history of Graves' disease with thyroid eye disease was treated with teprotumumab. She had a history of bilateral tinnitus and noticed a subjective improvement in her tinnitus after the second infusion. Audiology testing obtained before, during, and after completion of infusions showed symmetric and rapidly progressive worsening of the patient's sensorineural hearing loss. In contrast, a 42-year-old male with a history of Grave's disease endorsed worsening intermittent tinnitus and low-pitched hearing loss after initiation of teprotumumab. Audiology testing before, during, and after completion of infusions showed stable and normal hearing function bilaterally. CONCLUSION AND IMPORTANCE: This case series highlights the importance of objective testing in patients prior to and after teprotumumab initiation as subjective hearing changes may not accurately reflect objective hearing function. In addition, this report suggests that teprotumumab may play a role in potentiating sensorineural hearing loss.

CD47 expression and CD163+ macrophages correlated with prognosis of pancreatic neuroendocrine tumor.

BACKGROUND: Recent studies have suggested the important roles of CD47 and tumor-associated macrophages in the prognosis and immunotherapy of various human malignancies. However, the clinical significance of CD47 expression and CD163+ TAMs in pancreatic neuroendocrine tumor (PanNET) remains unclear. METHODS: In this study, 47 well-differentiated PanNET resection specimens were collected. CD47 expression and CD163+ macrophages were evaluated using immunohistochemistry and correlated with clinicopathologic properties. RESULTS: Positive CD47 staining was seen in all PanNETs as well as adjacent normal islets. Compared to normal islets, CD47 overexpressed in PanNETs (p = 0.0015). In the cohort, lymph node metastasis (LNM), lymphovascular invasion (LVI), and perineural invasion (PNI) were found in 36.2, 59.6, and 48.9% of the cases, respectively. Interestingly, PanNETs with LNM, LVI, or PNI had significantly lower H-score of CD47 than those without LNM (p = 0.035), LVI (p = 0.0005), or PNI (p = 0.0035). PanNETs in patients with disease progression (recurrence/death) also showed a significantly lower expression of CD47 than those without progression (p = 0.022). In contrast, CD163+ macrophage counts were significantly higher in cases with LNM, LVI, and PNI. CONCLUSIONS: Our data suggest relative low CD47 expression and high CD163+ TAMs may act as indicators for poor prognosis of PanNETs.

MEF2 transcription factors differentially contribute to retinal ganglion cell loss after optic nerve injury.

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies.

Orbital Actinomyces Masquerading as Meningioma.

Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and nonspecific findings on imaging and clinical examination, and frequently it can masquerade as other pathologies such as neoplasm and inflammatory disease. The authors present a case of actinomyces masquerading as meningioma with findings of hyperostosis and a superior orbital roof interosseous tract on imaging.

The Power of Patient Norms: Postoperative Pathway Associated With Shorter Hospital Stay After Free Autologous Breast Reconstruction.

INTRODUCTION: Enhanced recovery after surgery pathways designed to optimize postoperative care have become increasingly popular across multiple surgical specialties with proven benefits. In this retrospective cohort study, we present a comparative evaluation of the impact of protocol-based postoperative care on free autologous breast reconstruction patients. METHODS: With institutional review board approval, we performed a chart review of patients who underwent breast reconstruction with free autologous tissue transfer by a single surgeon from 2006 to 2017. Patients were managed according to a postoperative protocol since 2006 that initially called for discharge home on postoperative day (POD) 4 for unilateral cases and POD 5 for bilateral cases. In May 2015, the protocol was revised to discharge home on POD 3 for all cases. Patients who underwent reconstruction before (2006 to April 2015) and after (May 2015 to 2017) the change in postoperative protocol were compared. RESULTS: A total of 432 patients (647 breasts) underwent free autologous breast reconstruction during the study period. Flaps were predominantly muscle-sparing transverse rectus abdominis myocutaneous (56.3%) or deep inferior epigastric perforator (30.3%) flaps. Average patient age was 51.6 years (range, 29.7-80.3 years). Unilateral reconstructions were performed for 167 patients before and 50 patients after the protocol change; average hospital length of stay (LOS) was 4.5 and 3.4 days, respectively (P < 0.001). Bilateral reconstructions were performed for 153 patients before and 62 patients after the protocol change; average hospital LOS was 5.1 and 3.5 days, respectively (P < 0.001). There was no significant increase in patients with major or minor complications. CONCLUSIONS: Revising our postoperative protocol to reduce expected LOS was associated with an overall faster time to discharge without negative consequences in patients who underwent unilateral and bilateral free autologous breast reconstruction. Use of protocols to guide behavior not only can improve the patient experience by promoting a quicker return home, but may also have the added benefit of decreasing healthcare expenditures through reduced inpatient utilization.

Retinal Lesion Detection With Deep Learning Using Image Patches.

Purpose: To develop an automated method of localizing and discerning multiple types of findings in retinal images using a limited set of training data without hard-coded feature extraction as a step toward generalizing these methods to rare disease detection in which a limited number of training data are available. Methods: Two ophthalmologists verified 243 retinal images, labeling important subsections of the image to generate 1324 image patches containing either hemorrhages, microaneurysms, exudates, retinal neovascularization, or normal-appearing structures from the Kaggle dataset. These image patches were used to train one standard convolutional neural network to predict the presence of these five classes. A sliding window method was used to generate probability maps across the entire image. Results: The method was validated on the eOphta dataset of 148 whole retinal images for microaneurysms and 47 for exudates. A pixel-wise classification of the area under the curve of the receiver operating characteristic of 0.94 and 0.95, as well as a lesion-wise area under the precision recall curve of 0.86 and 0.64, was achieved for microaneurysms and exudates, respectively. Conclusions: Regionally trained convolutional neural networks can generate lesion-specific probability maps able to detect and distinguish between subtle pathologic lesions with only a few hundred training examples per lesion.

Slower saccadic reading in Parkinson's disease.

Idiopathic Parkinson's Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients but significantly correlated with age, duration of disease, and VFQ-25 scores. The presence of convergence insufficiency did not significantly correlate with reading time in PD patients, although on average there was slower reading time in those with convergence insufficiency by 8 s (p = 0.2613). We propose that a simple reading task using 120 single-digit numbers can be used as a screening tool in the clinical setting to assess functional ocular motor difficulties in Parkinson's disease that can have a profound impact on quality of life.

Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation.

Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.

Change in Lung Volume Following Thoracoscopic Anterior Spinal Fusion Surgery: A 3-Dimensional Computed Tomography Investigation.

STUDY DESIGN: Lung volumes and thoracic anatomy were measured from low-dose computed tomography (CT) scans preoperatively and 2 years following thoracoscopic anterior spinal fusion (TASF) for adolescent idiopathic scoliosis (AIS). OBJECTIVE: The aim of this study was to assess changes in lung volume after TASF surgical correction. SUMMARY OF BACKGROUND DATA: AIS patients are known to have decreased pulmonary function as a consequence of their spinal and ribcage deformity. Several studies have evaluated changes in pulmonary function clinically after scoliosis correction surgery showing varied results. To date, there have been no published studies using CT to evaluate lung volume changes following TASF. METHODS: Twenty-three female AIS patients with both pre- and 2 years postoperative low-dose CT scans were selected from an ethically approved, historical databank. Three-dimensional lung volumes were reconstructed to determine anatomical lung volumes. Right and left lung volumes, total lung volume, and right-to-left lung volume ratio were obtained as well as hemithoracic symmetry, to indicate the extent of thorax deformity. Cobb angle, rib hump, levels fused in surgery, and patient height were used for correlation analysis with the lung volume results. RESULTS: Left lung volume, total lung volume, and hemithoracic ratio all increased significantly 2 years after surgery. There was no significant change in right-to-left lung volume ratio (P = 0.36). Statistical regression found significant positive correlation between lung volume changes, reduction in Cobb angle, increase in height, and improvement in hemithoracic symmetry ratio. CONCLUSION: TASF resulted in a statistically significant increase in lung volume following surgery, as well as improvement in the symmetry of the thoracic architecture; however, the postoperative lung volumes remained in the lower 50th percentile relative to females without thoracic deformity. Furthermore, change in lung volume was significantly correlated with changes in Cobb angle, hemithoracic asymmetry, and increased patient height, which are important consequences of thoracic deformity correction surgery. LEVEL OF EVIDENCE: 3.

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

Abnormal eye movement behavior during reading in Parkinson's disease.

INTRODUCTION: Reading difficulties are common in Parkinson's disease (PD) but not well studied. We report a case of reading difficulties in a 40-year-old man with 6-year history of PD on dopamine replacement therapy. METHODS: We performed detailed neuro-ophthalmic examination and assessment of reading with and without infrared oculography. RESULTS: Clinical examination revealed visual acuity of 20/20, no evidence of vision loss, and normal eye movement and ocular alignment with normal saccades, pursuit, and normal convergence. During King-Devick test, a rapid number reading task performed on a book, patient had normal number reading speed. More detailed study of number and word reading using infrared oculography revealed that while this patient had normal speed and eye movement behavior during number reading, he had dramatic slowing and eye movement abnormality during word reading. The slower reading speed during word reading was due to increased number of progressive saccades, smaller saccade amplitudes, increased number of regressive saccades, and longer fixation durations. CONCLUSIONS: This case nicely illustrated the importance of comprehensive neuro-ophthalmic evaluations in Parkinson's disease and shows that reading difficulties can arise even when there is good visual acuity, ocular motor abilities necessary to read, and accommodation. In this case, reading difficulty was due to higher order ocular motor planning or cognitive abilities involved in word reading since the patient had no difficulty with ocular motor planning while reading numbers. These findings may have important implications towards our understanding of PD and can serve to spark further research in this important area.

Mutation Linked to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Reduces Low-Sensitivity α4ß2, and Increases α5α4ß2, Nicotinic Receptor Surface Expression.

A number of mutations in α4ß2-containing (α4ß2*) nicotinic acetylcholine (ACh) receptors (nAChRs) are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), including one in the ß2 subunit called ß2V287L. Two α4ß2* subtypes with different subunit stoichiometries and ACh sensitivities co-exist in the brain, a high-sensitivity subtype with (α4)2(ß2)3 subunit stoichiometry and a low-sensitivity subtype with (α4)3(ß2)2 stoichiometry. The α5 nicotinic subunit also co-assembles with α4ß2 to form a high-sensitivity α5α4ß2 nAChR. Previous studies suggest that the ß2V287L mutation suppresses low-sensitivity α4ß2* nAChR expression in a knock-in mouse model and also that α5 co-expression improves the surface expression of ADNFLE mutant nAChRs in a cell line. To test these hypotheses further, we expressed mutant and wild-type (WT) nAChRs in oocytes and mammalian cell lines, and measured the effects of the ß2V287L mutation on surface receptor expression and the ACh response using electrophysiology, a voltage-sensitive fluorescent dye, and superecliptic pHluorin (SEP). The ß2V287L mutation reduced the EC50 values of high- and low-sensitivity α4ß2 nAChRs expressed in Xenopus oocytes for ACh by a similar factor and suppressed low-sensitivity α4ß2 expression. In contrast, it did not affect the EC50 of α5α4ß2 nAChRs for ACh. Measurements of the ACh responses of WT and mutant nAChRs expressed in mammalian cell lines using a voltage-sensitive fluorescent dye and whole-cell patch-clamping confirm the oocyte data. They also show that, despite reducing the maximum response, ß2V287L increased the α4ß2 response to a sub-saturating ACh concentration (1 µM). Finally, imaging SEP-tagged α5, α4, ß2, and ß2V287L subunits showed that ß2V287L reduced total α4ß2 nAChR surface expression, increased the number of ß2 subunits per α4ß2 receptor, and increased surface α5α4ß2 nAChR expression. Thus, the ß2V287L mutation alters the subunit composition and sensitivity of α4ß2 nAChRs, and increases α5α4ß2 surface expression.

3D Pseudocontinuous arterial spin labeling in routine clinical practice: A review of clinically significant artifacts.

Arterial spin labeling (ASL) is a completely noninvasive magnetic resonance imaging (MRI) perfusion method for quantitatively measuring cerebral blood flow utilizing magnetically labeled arterial water. Advances in the technique have enabled the major MRI vendors to make the sequence available to the clinical neuroimaging community. Consequently, ASL is being increasingly incorporated into the routine neuroimaging protocol. Although a variety of ASL techniques are available, the ISMRM Perfusion Study Group and the European ASL in Dementia Consortium have released consensus guidelines recommending standardized implementation of 3D pseudocontinuous ASL with background suppression. The purpose of this review, aimed at the large number of neuroimaging clinicians who have either no or limited experience with this 3D pseudocontinuous ASL, is to discuss the common and clinically significant artifacts that may be encountered with this technique. While some of these artifacts hinder accurate interpretation of studies, either by degrading the images or mimicking pathology, there are other artifacts that are of clinical utility, because they increase the conspicuity of pathology. Cognizance of these artifacts will help the physician interpreting ASL to avoid potential diagnostic pitfalls, and increase their level of comfort with the technique.