Molecular Prosthetics for Long-Term Functional Imaging with Fluorescent Reporters

Abstract Background The evaluation of suspected ischaemic symptoms incorporates multi-modality anatomical and functional imaging tests. The 2016 update to the UK's NICE guidelines recommends CT coronary angiogram (CTCA) first line in patients without known coronary artery disease. Additive multi-modality functional imaging may provide synergistic diagnostic and prognostic information. Purpose To investigate the diagnostic accuracy, prognostic utility and cost of CTCA combined with subsequent multi-modality functional testing versus (vs) CTCA alone. Methods 772 consecutive patients were referred to a single UK tertiary centre with symptoms suggestive of ischaemia. 657 individuals (“CTCA group”) underwent CTCA alone, and 115 individuals (“Combined group”) underwent CTCA and then either perfusion cardiac MRI (n=25), stress echocardiogram (n=16), or myocardial perfusion scintigraphy (n=74). Patients underwent invasive angiography (n=79) +/− revascularisation at the discretion of the referring clinician. All readers and operators were aware of previous imaging findings. Revascularised patients (n=52) were excluded from long term follow-up. The remaining patients were followed-up for a mean of 38.1±17.4 months and the incidence of major adverse cardiovascular events (MACE) recorded. Costs were derived from the NICE guidelines. Results Baseline characteristics were similar between groups. The Combined group underwent significantly more invasive angiograms than the CTCA group (29.6% vs 6.8%, p=0.0001) with no significant difference in the rate of revascularisation (73% vs 67%, p=0.72). Mean time from CTCA to angiogram was significantly longer in the Combined group (81.2 vs 38.1 days, p=0.0001). Both sensitivity and specificity were lower in the Combined group than in the CTCA group (sensitivity: 70% vs 93%, specificity: 75% vs 100%). The rate of long term MACE was significantly higher in the Combined group (8.7% vs 2.6%, p=0.0026). Multivariate analysis of CTCA and functional imaging findings found that CTCA-derived four vessel aggregate stenosis score (0–12) was the strongest predictor of MACE for the whole cohort (OR 4.4, p<0.0001), and also for those with negative functional tests (OR 3.9, p<0.0001). Per patient, a combined strategy was more expensive than CTCA alone (£1551 vs £368, p=0.0001). CTCA and functional data vs outcomes Conclusions Combining multi-modality functional testing with CTCA increased costs but did not improve diagnostic accuracy or long term outcomes. Further reductions in both MACE and unnecessary invasive angiography are desirable; CT-derived functional data such as FFRCT may be implicated.

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Relative contribution of individual versus combined functional imaging studies in predicting seizure freedom in pediatric epilepsy surgery: an area under the curve analysis

Neurosurgical FOCUS ◽

10.3171/2020.1.focus19974 ◽

2020 ◽

Vol 48 (4) ◽

pp. E13

Author(s):

Pongkiat Kankirawatana ◽

Ismail S. Mohamed ◽

Jason Lauer ◽

Inmaculada Aban ◽

Hyunmi Kim ◽

...

Keyword(s):

Functional Imaging ◽

Surgical Outcomes ◽

Partial Epilepsy ◽

Curve Analysis ◽

Imaging Modalities ◽

Pediatric Epilepsy ◽

Seizure Freedom ◽

Relative Contribution ◽

Refractory Partial Epilepsy

OBJECTIVEThe goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors’ institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy.METHODSThis was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography–magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes.RESULTSThere was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions.CONCLUSIONSComprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

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Long term functional plasticity of sensory inputs mediated by olfactory learning

eLife ◽

10.7554/elife.02109 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 32

Author(s):

Nixon M Abraham ◽

Roberto Vincis ◽

Samuel Lagier ◽

Ivan Rodriguez ◽

Alan Carleton

Keyword(s):

Functional Imaging ◽

Olfactory System ◽

Sensory Input ◽

Adult Mouse ◽

Functional Plasticity ◽

Sensory Inputs ◽

Sensory Pathways ◽

Input Activity ◽

Odor Exposure

Sensory inputs are remarkably organized along all sensory pathways. While sensory representations are known to undergo plasticity at the higher levels of sensory pathways following peripheral lesions or sensory experience, less is known about the functional plasticity of peripheral inputs induced by learning. We addressed this question in the adult mouse olfactory system by combining odor discrimination studies with functional imaging of sensory input activity in awake mice. Here we show that associative learning, but not passive odor exposure, potentiates the strength of sensory inputs up to several weeks after the end of training. We conclude that experience-dependent plasticity can occur in the periphery of adult mouse olfactory system, which should improve odor detection and contribute towards accurate and fast odor discriminations.

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Plasticity and the Human Brain: Insights from Functional Imaging

The Neuroscientist ◽

10.1177/107385849600200613 ◽

1996 ◽

Vol 2 (6) ◽

pp. 353-362 ◽

Cited By ~ 10

Author(s):

Richard S.J. Frackowiak

Keyword(s):

Human Brain ◽

Functional Imaging ◽

Large Scale ◽

Imaging Techniques ◽

Functional Reorganization ◽

Neuronal Populations ◽

Normal Behavior ◽

Definition Of ◽

The Brain

This article begins with a definition of cerebral plasticity in human brain that rests on the concept of a long-term alteration in patterns of task- or behavior-related activity in distributed brain systems. The theme is then developed to show how such a concept and the mechanisms it implies can be investigated and mapped using modern noninvasive functional imaging techniques. The human experimental literature is critically presented in relation to normal behavior, especially in relation to the acquisition of motor skills and learning. A discussion of the functional reorganization that follows brain injury and that is associated with spontaneous recovery from motor and perceptual deficits is then presented from the perspective of understanding the brain mechanisms at the level of large-scale neuronal populations.

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Functional Imaging Changes in the Medial Prefrontal Cortex in Adult ADHD

Journal of Attention Disorders ◽

10.1177/1087054715611492 ◽

2015 ◽

Vol 22 (7) ◽

pp. 679-693 ◽

Cited By ~ 11

Author(s):

José Salavert ◽

Josep A. Ramos-Quiroga ◽

Ana Moreno-Alcázar ◽

Xavier Caseras ◽

Gloria Palomar ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Functional Imaging ◽

Default Mode Network ◽

Adult Adhd ◽

Control Group ◽

Default Mode ◽

Long Term Treatment ◽

Back Task

Objective: Functional imaging studies have found reduced frontal activity, mainly in dorso/ventro-lateral regions and reduced task-related de-activation of the default mode network in childhood ADHD. Adult studies are fewer and inconclusive. We aimed to investigate the potential neural bases of executive function in ADHD adults, examining brain activity during N-back task performance, and to explore the potential corrective effects of long-term methylphenidate treatment. Method: We recruited a large adult ADHD-combined sample and a matched control group and obtained functional magnetic resonance imaging (fMRI) images during task. ADHD participants were subdivided in a group under long-term treatment with methylphenidate (washed out for the scan) and a treatment-naive group. Results: ADHD participants showed deficient de-activation of the medial prefrontal cortex during 2-back task, implying default mode network dysfunction. We found no relationship between blunted de-activation and treatment history. Conclusion: As de-activation failure in the medial frontal cortex is linked to lapses of attention, findings suggest a potential link to ADHD symptomatology.

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Management of early-stage Hodgkin lymphoma: is there still a role for radiation?

Hematology ◽

10.1182/asheducation-2013.1.400 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 400-405 ◽

Cited By ~ 5

Author(s):

Peter W. M. Johnson

Keyword(s):

Hodgkin Lymphoma ◽

Functional Imaging ◽

Combination Chemotherapy ◽

Early Stage ◽

Early Stage Disease ◽

Stage Disease ◽

Highly Effective ◽

Cure Rates

Abstract Although radiotherapy is highly effective for the treatment of Hodgkin lymphoma, the realization of its potential long-term toxicity and the demonstration of excellent results from combination chemotherapy have led to a retreat from its use in early-stage disease. Recent trials using functional imaging may allow better identification of those patients for whom radiotherapy may be safely omitted without compromising cure rates and this review examines the evidence for this.

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One month in the life of a neuron: longitudinal single-unit electrophysiology in the monkey visual system

Journal of Neurophysiology ◽

10.1152/jn.00052.2014 ◽

2014 ◽

Vol 112 (7) ◽

pp. 1748-1762 ◽

Cited By ~ 29

Author(s):

David B. T. McMahon ◽

Igor V. Bondar ◽

Olusoji A. T. Afuwape ◽

David C. Ide ◽

David A. Leopold

Keyword(s):

Functional Imaging ◽

Single Unit ◽

Large Scale ◽

Interspike Interval ◽

Single Neurons ◽

Visual Responses ◽

Image Libraries ◽

Behaving Monkeys ◽

Spike Waveforms

Conventional recording methods generally preclude following the activity of the same neurons in awake animals across days. This limits our ability to systematically investigate the principles of neuronal specialization, or to study phenomena that evolve over multiple days such as experience-dependent plasticity. To redress this shortcoming, we developed a drivable, chronically implanted microwire recording preparation that allowed us to follow visual responses in inferotemporal (IT) cortex in awake behaving monkeys across multiple days, and in many cases across months. The microwire bundle and other implanted components were MRI compatible and thus permitted in the same animals both functional imaging and long-term recording from multiple neurons in deep structures within a region the approximate size of one voxel (<1 mm). The distinct patterns of stimulus selectivity observed in IT neurons, together with stable features in spike waveforms and interspike interval distributions, allowed us to track individual neurons across weeks and sometimes months. The long-term consistency of visual responses shown here permits large-scale mappings of neuronal properties using massive image libraries presented over the course of days. We demonstrate this possibility by screening the visual responses of single neurons to a set of 10,000 stimuli.

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