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1.  Biomagnetic signatures of uncoupled gastric musculature 
Gastric slow waves propagate in the electrical syncytium of the healthy stomach, being generated at a rate of approximately three times per minute in a pacemaker region along the greater curvature of the antrum and propagating distally towards the pylorus. Disease states are known to alter the normal gastric slow wave. Recent studies have suggested the use of biomagnetic techniques for assessing parameters of the gastric slow wave that have potential diagnostic significance. We present a study in which the gastric syncytium was uncoupled by mechanical division as we recorded serosal electric potentials along with multichannel biomagnetic signals and cutaneous potentials. By computing the surface current density (SCD) from multichannel biomagnetic recordings, we were able to quantify gastric slow wave propagation as well as the frequency and amplitude of the slow wave and to show that these correlate well with similar parameters from serosal electrodes. We found the dominant slow wave frequency to be an unreliable indicator of gastric uncoupling as uncoupling results in the appearance of multiple slow wave sources at various frequencies in external recordings. The percentage of power distributed in specific frequency ranges exhibited significant postdivision changes. Propagation velocity determined from SCD maps was a weak indicator of uncoupling in this work; we believe that the relatively low spatial resolution of our 19-channel biomagnetometer confounds the characterization of spatial variations in slow wave propagation velocities. Nonetheless, the biomagnetic technique represents a non-invasive method for accurate determination of clinically significant parameters of the gastric slow wave.
PMCID: PMC2855967  PMID: 19222760
electrogastrography; gastric slow wave; magnetogastrography; SQUID magnetometer
2.  Differentiation of myomas by means of biomagnetic and doppler findings 
To elucidate the hemodynamics of the uterine artery myomas by use of Doppler ultrasound and biomagnetic measurements.
Twenty-four women were included in the study. Sixteen of them were characterised with large myomas whereas 8 of them with small ones. Biomagnetic signals of uterine arteries myomas were recorded and analyzed with Fourier analysis. The biomagnetic signals were distributed according to spectral amplitudes as high (140–300 ft/√Hz), low (50–110 ft/√Hz) and borderline (111–139 ft/√Hz). Uterine artery waveform measurements were evaluated by use of Pulsatility Index (PI) (normal value PI < 1.45).
There was a statistically significant difference between large and small myomas concerning the waveform amplitudes (P < 0.0005) and the PI index (P < 0.0005). Specifically, we noticed high biomagnetic amplitudes in most large myomas (93.75 %) and low biomagnetic amplitudes in most small ones (87.5 %).
It is suggested that the biomagnetic recordings of uterine artery myomas could be a valuable modality in the estimation of the circulation of blood cells justifying the findings of Doppler velocimetry examination.
PMCID: PMC1450278  PMID: 16584560
3.  Noninvasive assessment of the effects of glucagon on the gastric slow wave 
Hyperglycemic effects on the gastric slow wave are not well understood, and no studies have examined the effects that hyperglycemia has on gastric slow wave magnetic fields. We recorded multichannel magnetogastrograms (MGGs) before and after intravenous administration of glucagon and subsequent modest hyperglycemia in 20 normal volunteers. Normal slow waves were evident in baseline MGG recordings from all 20 subjects, but within 15 minutes after glucagon had been given, we noted significant effects on MGG signals. In addition to an overall decrease in the slow wave frequency from 2.9 ± 0.5 cycles per minute (cpm) to 2.2 ± 0.1 cpm (p < 0.05), we observed significant changes in the number and range of spectral peaks recorded. Furthermore, the propagation velocity determined from surface current density maps computed from the multichannel MGG decreased significantly (7.1 ± 0.8 mm/s to 5.0 ± 0.3 mm/s, p < 0.05). This is the first study of biomagnetic effects of hyperglycemia in normal subjects. Our results suggest that the analysis of the magnetogastrogram provides parameter quantification for gastric electrical activity specific to and characteristic of slow wave abnormalities associated with increased serum glucose by injection of glucagon.
PMCID: PMC2726773  PMID: 17884978
4.  Surface Current Density Mapping for Identification of Gastric Slow Wave Propagation 
The magnetogastrogram records clinically relevant parameters of the electrical slow wave of the stomach noninvasively. Besides slow wave frequency, gastric slow wave propagation velocity is a potentially useful clinical indicator of the state of health of gastric tissue, but it is a difficult parameter to determine from noninvasive bioelectric or biomagnetic measurements. We present a method for computing the surface current density (SCD) from multichannel magnetogastrogram recordings that allows computation of the propagation velocity of the gastric slow wave. A moving dipole source model with hypothetical as well as realistic biomagnetometer parameters demonstrates that while a relatively sparse array of magnetometer sensors is sufficient to compute a single average propagation velocity, more detailed information about spatial variations in propagation velocity requires higher density magnetometer arrays. Finally, the method is validated with simultaneous MGG and serosal EMG measurements in a porcine subject.
PMCID: PMC2722927  PMID: 19403355
biomagnetism; current dipole; electrogastrogram; magnetogastrogram; SQUID magnetometer
5.  Histostitcher™: An informatics software platform for reconstructing whole-mount prostate histology using the extensible imaging platform framework 
Co-registration of ex-vivo histologic images with pre-operative imaging (e.g., magnetic resonance imaging [MRI]) can be used to align and map disease extent, and to identify quantitative imaging signatures. However, ex-vivo histology images are frequently sectioned into quarters prior to imaging.
This work presents Histostitcher™, a software system designed to create a pseudo whole mount histology section (WMHS) from a stitching of four individual histology quadrant images.
Materials and Methods:
Histostitcher™ uses user-identified fiducials on the boundary of two quadrants to stitch such quadrants. An original prototype of Histostitcher™ was designed using the Matlab programming languages. However, clinical use was limited due to slow performance, computer memory constraints and an inefficient workflow. The latest version was created using the extensible imaging platform (XIP™) architecture in the C++ programming language. A fast, graphics processor unit renderer was designed to intelligently cache the visible parts of the histology quadrants and the workflow was significantly improved to allow modifying existing fiducials, fast transformations of the quadrants and saving/loading sessions.
The new stitching platform yielded significantly more efficient workflow and reconstruction than the previous prototype. It was tested on a traditional desktop computer, a Windows 8 Surface Pro table device and a 27 inch multi-touch display, with little performance difference between the different devices.
Histostitcher™ is a fast, efficient framework for reconstructing pseudo WMHS from individually imaged quadrants. The highly modular XIP™ framework was used to develop an intuitive interface and future work will entail mapping the disease extent from the pseudo WMHS onto pre-operative MRI.
PMCID: PMC4023035  PMID: 24843820
Computer aided diagnosis; prostate histology; extensible imaging platform
6.  Saturated linkage map construction in Rubus idaeus using genotyping by sequencing and genome-independent imputation 
BMC Genomics  2013;14:2.
Rapid development of highly saturated genetic maps aids molecular breeding, which can accelerate gain per breeding cycle in woody perennial plants such as Rubus idaeus (red raspberry). Recently, robust genotyping methods based on high-throughput sequencing were developed, which provide high marker density, but result in some genotype errors and a large number of missing genotype values. Imputation can reduce the number of missing values and can correct genotyping errors, but current methods of imputation require a reference genome and thus are not an option for most species.
Genotyping by Sequencing (GBS) was used to produce highly saturated maps for a R. idaeus pseudo-testcross progeny. While low coverage and high variance in sequencing resulted in a large number of missing values for some individuals, a novel method of imputation based on maximum likelihood marker ordering from initial marker segregation overcame the challenge of missing values, and made map construction computationally tractable. The two resulting parental maps contained 4521 and 2391 molecular markers spanning 462.7 and 376.6 cM respectively over seven linkage groups. Detection of precise genomic regions with segregation distortion was possible because of map saturation. Microsatellites (SSRs) linked these results to published maps for cross-validation and map comparison.
GBS together with genome-independent imputation provides a rapid method for genetic map construction in any pseudo-testcross progeny. Our method of imputation estimates the correct genotype call of missing values and corrects genotyping errors that lead to inflated map size and reduced precision in marker placement. Comparison of SSRs to published R. idaeus maps showed that the linkage maps constructed with GBS and our method of imputation were robust, and marker positioning reliable. The high marker density allowed identification of genomic regions with segregation distortion in R. idaeus, which may help to identify deleterious alleles that are the basis of inbreeding depression in the species.
PMCID: PMC3575332  PMID: 23324311
Genotyping by sequencing; GBS; RADseq; Imputation; Raspberry; Rubus idaeus; Psuedotestcross; Linkage map; Segregation distortion
7.  Perception of acoustically complex phonological features in vowels is reflected in the induced brain-magnetic activity 
A central issue in speech recognition is which basic units of speech are extracted by the auditory system and used for lexical access. One suggestion is that complex acoustic-phonetic information is mapped onto abstract phonological representations of speech and that a finite set of phonological features is used to guide speech perception. Previous studies analyzing the N1m component of the auditory evoked field have shown that this holds for the acoustically simple feature place of articulation. Brain magnetic correlates indexing the extraction of acoustically more complex features, such as lip rounding (ROUND) in vowels, have not been unraveled yet. The present study uses magnetoencephalography (MEG) to describe the spatial-temporal neural dynamics underlying the extraction of phonological features. We examined the induced electromagnetic brain response to German vowels and found the event-related desynchronization in the upper beta-band to be prolonged for those vowels that exhibit the lip rounding feature (ROUND). It was the presence of that feature rather than circumscribed single acoustic parameters, such as their formant frequencies, which explained the differences between the experimental conditions. We conclude that the prolonged event-related desynchronization in the upper beta-band correlates with the computational effort for the extraction of acoustically complex phonological features from the speech signal. The results provide an additional biomagnetic parameter to study mechanisms of speech perception.
PMCID: PMC1892031  PMID: 17543108
8.  Sciatica: Detection and Confirmation by New Method 
We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--“mechanosensitized,” as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further.
Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG.
Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the nerve and relieve pain moment we desensitize the nerve.
PMCID: PMC4325484
sciatica; mechano sensitization; Inflammation; chemical; stretch sensitivity; pseudo unipolar axon; selective nerve root block; distal block; palpation of nerve
9.  Biomagnetic techniques for evaluating gastric emptying, peristaltic contraction and transit time 
Biomagnetic techniques were used to measure motility in various parts of the gastrointestinal (GI) tract, particularly a new technique for detecting magnetic markers and tracers. A coil was used to enhance the signal from a magnetic tracer in the GI tract and the signal was detected using a fluxgate magnetometer or a magnetoresistor in an unshielded room. Estimates of esophageal transit time were affected by the position of the subject. The reproducibility of estimates derived using the new biomagnetic technique was greater than 85% and it yielded estimates similar to those obtained using scintigraphy. This technique is suitable for studying the effect of emotional state on GI physiology and for measuring GI transit time. The biomagnetic technique can be used to evaluate digesta transit time in the esophagus, stomach and colon, peristaltic frequency and gastric emptying and is easy to use in the hospital setting.
PMCID: PMC3196621  PMID: 22025978
Biomagnetic techniques; Magnetogastrography; Gastric emptying; Scintigraphy; Peristaltic contractions
10.  Nonlinear analysis of biomagnetic signals recorded from uterine myomas 
To determine if there is any non-linearity in the biomagnetic recordings of uterine myomas and to find any differences that may be present in the mechanisms underlying their signal dynamics.
Twenty-four women were included in the study. Sixteen of them were characterised with large myomas and 8 with small ones. Uterine artery waveform measurements were evaluated by use of Pulsatility Index (PI) (normal value PI<1.45).
Applying nonlinear analysis to the biomagnetic signals of the uterine myomas, we observed a clear saturation value for the group of large ones (mean = 11.35 ± 1.49) and no saturation for the small ones.
The comparison of the saturation values in the biomagnetic recordings of large and small myomas may be a valuable tool in the evaluation of functional changes in their dynamic behavior.
PMCID: PMC1484479  PMID: 16571144
11.  SoftWAXS: a computational tool for modeling wide-angle X-ray solution scattering from biomolecules 
Journal of Applied Crystallography  2009;42(Pt 5):932-943.
An accurate numerical approach has been implemented for calculating wide-angle X-ray solution scattering patterns of proteins using the traditional scattering model that treats water as a continuum. The results suggest that, at wide angles, the excluded-volume and solvation-layer contributions to scattering cannot be reliably estimated using the continuum representation.
This paper describes a computational approach to estimating wide-angle X-ray solution scattering (WAXS) from proteins, which has been implemented in a computer program called SoftWAXS. The accuracy and efficiency of SoftWAXS are analyzed for analytically solvable model problems as well as for proteins. Key features of the approach include a numerical procedure for performing the required spherical averaging and explicit representation of the solute–solvent boundary and the surface of the hydration layer. These features allow the Fourier transform of the excluded volume and hydration layer to be computed directly and with high accuracy. This approach will allow future investigation of different treatments of the electron density in the hydration shell. Numerical results illustrate the differences between this approach to modeling the excluded volume and a widely used model that treats the excluded-volume function as a sum of Gaussians representing the individual atomic excluded volumes. Comparison of the results obtained here with those from explicit-solvent molecular dynamics clarifies shortcomings inherent to the representation of solvent as a time-averaged electron-density profile. In addition, an assessment is made of how the calculated scattering patterns depend on input parameters such as the solute-atom radii, the width of the hydration shell and the hydration-layer contrast. These results suggest that obtaining predictive calculations of high-resolution WAXS patterns may require sophisticated treatments of solvent.
PMCID: PMC3041499  PMID: 21339902
small-angle X-ray scattering (SAXS); wide-angle X-ray scattering (WAXS); proteins; SoftWAXS; computer programs
12.  Feeling before knowing why: The role of the orbitofrontal cortex in intuitive judgments—an MEG study 
In theory, intuitive decisions are made immediately, without conscious, reasoned thought. They are experienced as decisions based on hunches that cannot be explicitly described but, nevertheless, guide subsequent action. Investigating the underlying neural mechanisms, previous research has found the orbitofrontal cortex (OFC) to be crucial to intuitive processes, but its specific role has remained unclear. On the basis of a two-stage conceptualization of intuition suggested by Bowers, Regehr, Balthazard, and Parker Cognitive Psychology, 22, 72-110 (1990), we attempt to clarify the OFC’s role in intuitive processing. We propose that it functions as an early integrator of incomplete stimulus input guiding subsequent processing by means of a coarse representation of the gist of the information. On the subjective level, this representation would be perceived as a (gut) feeling biasing the decision. Our aim in the present study was to test this neural model and rule out alternative explanations of OFC activation in intuitive judgments. We used magnetoencephalography (MEG) to record participants' electromagnetic brain responses during a visual coherence judgment task. As in earlier studies, the OFC was found to be activated when participants perceived coherence. Using MEG, it could be shown that this increase in activation began earlier in the OFC than in temporal object recognition areas. Moreover, the present study demonstrated that OFC activation was independent of physical stimulus characteristics, task requirements, and participants’ explicit recognition of the stimuli presented. These results speak to the OFC’s fundamental role in the early steps of intuitive judgments and suggest the proposed neural model as a promising starting point for future investigations.
PMCID: PMC4218982  PMID: 24789812
Decision making; Intuition; Coherence judgments; Orbitofrontal cortex; Magnetoencephalography
13.  Integration of the OpenIGTLink Network Protocol for Image-Guided Therapy with the Medical Platform MeVisLab 
We present the integration of the OpenIGTLink network protocol for image-guided therapy (IGT) with the medical prototyping platform MeVisLab. OpenIGTLink is a new, open, simple and extensible network communication protocol for IGT. The protocol provides a standardized mechanism to connect hardware and software by the transfer of coordinate transforms, images, and status messages. MeVisLab is a framework for the development of image processing algorithms and visualization and interaction methods, with a focus on medical imaging. The integration of OpenIGTLink into MeVisLab has been realized by developing a software module using the C++ programming language. As a result, researchers using MeVisLab can interface their software to hardware devices that already support the OpenIGTLink protocol, such as the NDI Aurora magnetic tracking system. In addition, the OpenIGTLink module can also be used to communicate directly with Slicer, a free, open source software package for visualization and image analysis. The integration has been tested with tracker clients available online and a real tracking system.
OpenIGTLink is a new, open, simple and extensible network communication protocol for image-guided therapy (IGT). The protocol provides a standardized mechanism to connect hardware and software by the transfer of coordinate transforms, images, and status messages. MeVisLab is a framework for the development of image processing algorithms and visualization and interaction methods, with a focus on medical imaging.
We present the integration of the OpenIGTLink network protocol for IGT with the medical prototyping platform MeVisLab. The integration of OpenIGTLink into MeVisLab has been realized by developing a software module using the C++ programming language.
The presented integration was evaluated with tracker clients that are available online. Furthermore, the integration was used to connect MeVisLab to Slicer and a NDI tracking system over the network. We also measured the latency time during navigation with a real instrument to show that the integration can be used clinically.
Researchers using MeVisLab can interface their software to hardware devices that already support the OpenIGTLink protocol, such as the NDI Aurora magnetic tracking system. In addition, the OpenIGTLink module can also be used to communicate directly with Slicer, a free, open source software package for visualization and image analysis.
PMCID: PMC3405168  PMID: 22374845
OpenIGTLink; MeVisLab; image-guided therapy; surgical navigation; system; Slicer
14.  Assessment of Scanning Tunneling Spectroscopy Modes Inspecting Electron Confinement in Surface-Confined Supramolecular Networks 
Scientific Reports  2013;3:1454.
Scanning tunneling spectroscopy (STS) enables the local, energy-resolved investigation of a samples surface density of states (DOS) by measuring the differential conductance (dI/dV) being approximately proportional to the DOS. It is popular to examine the electronic structure of elementary samples by acquiring dI/dV maps under constant current conditions. Here we demonstrate the intricacy of STS mapping of samples exhibiting a strong corrugation originating from electronic density and local work function changes. The confinement of the Ag(111) surface state by a porous organic network is studied with maps obtained under constant-current (CC) as well as open-feedback-loop (OFL) conditions. We show how the CC maps deviate markedly from the physically more meaningful OFL maps. By applying a renormalization procedure to the OFL data we can mimic the spurious effects of the CC mode and thereby rationalize the physical effects evoking the artefacts in the CC maps.
PMCID: PMC3600600  PMID: 23503526
15.  Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors 
Sensors (Basel, Switzerland)  2009;9(4):2976-2999.
Biomagnetic nano and microparticles platforms have attracted considerable interest in the field of biological sensors due to their interesting physico-chemical properties, high specific surface area, good mechanical stability and opportunities for generating magneto-switchable devices. This review discusses recent advances in the development and characterization of active biomagnetic nanoassemblies, their interaction with biological molecules and their use in bioanalytical sensors.
PMCID: PMC3348820  PMID: 22574058
Biomagnetic materials; composite magnetic materials; bio-immobilization; biological sensors
16.  Substrate Three-Dimensionality Induces Elemental Morphological Transformation of Sensory Neurons on a Physiologic Timescale 
Tissue Engineering. Part A  2011;18(1-2):93-102.
The natural environment of a neuron is the three-dimensional (3D) tissue. In vivo, embryonic sensory neurons transiently express a bipolar morphology with two opposing neurites before undergoing cytoplasmic and cytoskeletal rearrangement to a more mature pseudo-unipolar axonal arbor before birth. The unipolar morphology is crucial in the adult for correct information transmission from the periphery to the central nervous system. On two-dimensional (2D) substrates this transformation is delayed significantly or absent. We report that a 3D culture platform can invoke the characteristic transformation to the unipolar axonal arbor within a time frame similar to in vivo, overcoming the loss of this essential milestone in 2D substrates. Additionally, 3D substrates alone provided an environment that promoted axonal branching features that reflect morphological patterns observed in vivo. We have also analyzed the involvement of soluble cues in these morphogenic processes by culturing the neurons in the presence and absence of nerve growth factor (NGF), a molecule that plays distinct roles in the development of the peripheral and central nervous systems. Without NGF, both 2D and 3D cultures had significant decreases in the relative population of unipolar neurons as well as shorter neurite lengths and fewer branch points compared to cultures with NGF. Interestingly, branching features of neurons cultured in 3D without NGF resemble those of neurons cultured in 2D with NGF. Therefore, neurons cultured in 3D without NGF lost the ability to differentiate into unipolar neurons, suggesting that this morphological hallmark requires not only presentation of soluble cues like NGF, but also the surrounding 3D presentation of adhesive ligands to allow for realization of the innate morphogenic program. We propose that in a 3D environment, various matrix and soluble cues are presented toward all surfaces of the cell; this optimized milieu allows neurons to elaborate their genuine phenotype and follow programmed instructions that are intrinsic to the neuron, but disrupted when cells were dissected from the embryo. Thus, this study presents quantitative data supporting that 3D substrates are critical for sustaining the in vivo ontogeny of neurons and deciphering signaling mechanisms necessary for designing biomaterial scaffolds for nerve generation and repair.
PMCID: PMC3246411  PMID: 21910606
17.  Functional Brain Imaging 
Executive Summary
The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD).
Clinical Need: Target Population and Condition
Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006.
In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging.
Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci.
Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people.
Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy.
The Technology Being Reviewed
Functional Brain Imaging
Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex.
In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application.
Review Strategy
The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers.
General inclusion criteria were applied to all conditions. Those criteria included the following:
Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies.
Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).
English-language studies.
Human studies.
Any age.
Studying at least one of the following: fMRI, PET, MRS, or MEG.
Functional brain imaging modality must be compared with a clearly defined reference standard.
Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost.
Summary of Findings
There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients.
The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results.
The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another.
There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research.
Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG.
The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG.
There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy.
Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients.
There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS.
PMCID: PMC3379170  PMID: 23074493
18.  Effects of anatomical position on esophageal transit time: A biomagnetic diagnostic technique 
AIM: To study the esophageal transit time (ETT) and compare its mean value among three anatomical inclinations of the body; and to analyze the correlation of ETT to body mass index (BMI).
METHODS: A biomagnetic technique was implemented to perform this study: (1) The transit time of a magnetic marker (MM) through the esophagus was measured using two fluxgate sensors placed over the chest of 14 healthy subjects; (2) the ETT was assessed in three anatomical positions (at upright, fowler, and supine positions; 90º, 45º and 0º, respectively).
RESULTS: ANOVA and Tuckey post-hoc tests demonstrated significant differences between ETT mean of the different positions. The ETT means were 5.2 ± 1.1 s, 6.1 ± 1.5 s, and 23.6 ± 9.2 s for 90º, 45º and 0º, respectively. Pearson correlation results were r = -0.716 and P < 0.001 by subjects’ anatomical position, and r = -0.024 and P > 0.05 according the subject’s BMI.
CONCLUSION: We demonstrated that using this biomagnetic technique, it is possible to measure the ETT and the effects of the anatomical position on the ETT.
PMCID: PMC2748206  PMID: 18837088
Transit time; Magnetic marker; Esophagus; Anatomical position; Non-invasive
19.  Mean Apparent Propagator (MAP) MRI: a novel diffusion imaging method for mapping tissue microstructure 
NeuroImage  2013;78:16-32.
Diffusion-weighted magnetic resonance (MR) signals reflect information about underlying tissue microstructure and cytoarchitecture. We propose a quantitative, efficient, and robust mathematical and physical framework for representing diffusion-weighted MR imaging (MRI) data obtained in “q-space,” and the corresponding “mean apparent propagator (MAP)” describing molecular displacements in “r-space.” We also define and map novel quantitative descriptors of diffusion that can be computed robustly using this MAP-MRI framework.
We describe efficient analytical representation of the three-dimensional q-space MR signal in a series expansion of basis functions that accurately describes diffusion in many complex geometries. The lowest order term in this expansion contains a diffusion tensor that characterizes the Gaussian displacement distribution, equivalent to diffusion tensor MRI (DTI). Inclusion of higher order terms enables the reconstruction of the true average propagator whose projection onto the unit “displacement” sphere provides an orientational distribution function (ODF) that contains only the orientational dependence of the diffusion process. The representation characterizes novel features of diffusion anisotropy and the non-Gaussian character of the three-dimensional diffusion process. Other important measures this representation provides include the return-to-the-origin probability (RTOP), and its variants for diffusion in one- and two-dimensions—the return-to-the-plane probability (RTPP), and the return-to-the-axis probability (RTAP), respectively. These zero net displacement probabilities measure the mean compartment (pore) volume and cross-sectional area in distributions of isolated pores irrespective of the pore shape.
MAP-MRI represents a new comprehensive framework to model the three-dimensional q-space signal and transform it into diffusion propagators. Experiments on an excised marmoset brain specimen demonstrate that MAP-MRI provides several novel, quantifiable parameters that capture previously obscured intrinsic features of nervous tissue microstructure. This should prove helpful for investigating the functional organization of normal and pathologic nervous tissue.
PMCID: PMC4059870  PMID: 23587694
diffusion; propagator; ODF; return-to-origin; non-Gaussianity; anisotropy; volume; Hermite; SHORE; generalized DTI; GDTI
20.  Developmentally Regulated SCN5A Splice Variant Potentiates Dysfunction of a Novel Mutation Associated with Severe Fetal Arrhythmia 
Heart Rhythm  2011;9(4):590-597.
Congenital long-QT syndrome (LQTS) may present during fetal development and can be life-threatening. The molecular mechanism for the unusual early onset of LQTS during fetal development is unknown.
We sought to elucidate the molecular basis for severe fetal LQTS presenting at 19-weeks gestation, the earliest known presentation of this disease.
Fetal magnetocardiography was used to demonstrated torsade de pointes and a prolonged rate-corrected QT interval. In vitro electrophysiological studies were performed to determine functional consequences of a novel SCN5A mutation found in the fetus.
The fetus presented with episodes of ventricular ectopy progressing to incessant ventricular tachycardia and hydrops fetalis. Genetic analysis disclosed a novel, de novo heterozygous mutation in SCN5A (L409P) and a homozygous common variant (R558). In vitro electrophysiological studies demonstrated that the mutation in combination with R558 caused significant depolarized shifts in voltage-dependence of inactivation and activation, faster recovery from inactivation and a 7-fold greater level of persistent current. When the mutation was engineered in a fetal-expressed SCN5A splice isoform, channel dysfunction was markedly potentiated. Also, R558 alone in the fetal splice isoform evoked a large persistent current, hence both alleles were dysfunctional.
We report the earliest confirmed diagnosis of symptomatic LQTS, and present evidence that mutant cardiac sodium channel dysfunction is potentiated by a developmentally regulated alternative splicing event in SCN5A. Our findings provide a plausible mechanism for the unusual severity and early onset of cardiac arrhythmia in fetal LQTS.
PMCID: PMC3292693  PMID: 22064211
arrhythmia; sodium channel; SCN5A; sudden death; long-QT syndrome; magnetocardiography; alternative splicing
21.  Advances in BAC-Based Physical Mapping and Map Integration Strategies in Plants 
In the advent of next-generation sequencing (NGS) platforms, map-based sequencing strategy has been recently suppressed being too expensive and laborious. The detailed studies on NGS drafts alone indicated these assemblies remain far from gold standard reference quality, especially when applied on complex genomes. In this context the conventional BAC-based physical mapping has been identified as an important intermediate layer in current hybrid sequencing strategy. BAC-based physical map construction and its integration with high-density genetic maps have benefited from NGS and high-throughput array platforms. This paper addresses the current advancements of BAC-based physical mapping and high-throughput map integration strategies to obtain densely anchored well-ordered physical maps. The resulted maps are of immediate utility while providing a template to harness the maximum benefits of the current NGS platforms.
PMCID: PMC3303678  PMID: 22500080
22.  Intra- and multicenter reproducibility of pulsed, continuous and pseudo-continuous arterial spin labeling methods for measuring cerebral perfusion 
Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P<0.05). Pseudo-continuous ASL and multi TI PASL varied least between sites. Variability maps of all methods showed most variability near brain-feeding arteries within sessions and in gray matter between sessions. On the basis of the results of this study, one could consider the use of reference values in clinical routine, with whole-brain p-CASL perfusion varying <20% over repeated measurements within the same individuals considered to be normal. Knowledge on regional variability allows for the use of perfusion-weighted images in the assessment of local cerebral pathology.
PMCID: PMC3170937  PMID: 21304555
arterial spin labeling; multicenter; reference values; regional variability; reproducibility
23.  Evaluation of Two Approaches for Aligning Data Obtained from a Motion Capture System and an In-Shoe Pressure Measurement System 
Sensors (Basel, Switzerland)  2014;14(9):16994-17007.
An in-shoe pressure measurement (IPM) system can be used to measure center of pressure (COP) locations, and has fewer restrictions compared to the more conventional approach using a force platform. The insole of an IPM system, however, has its own coordinate system. To use an IPM system along with a motion capture system, there is thus a need to align the coordinate systems of the two measurement systems. To address this need, the current study examined two different approaches—rigid body transformation and nonlinear mapping (i.e., multilayer feed-forward neural network (MFNN))—to express COP measurements from an IPM system in the coordinate system of a motion capture system. Ten participants (five male and five female) completed several simulated manual material handling (MMH) activities, and during these activities the performance of the two approaches was assessed. Results indicated that: (1) performance varied between MMH activity types; and (2) a MFNN performed better than or comparable to the rigid body transformation, depending on the specific input variable sets used. Further, based on the results obtained, it was argued that a nonlinear mapping vs. rigid body transformation approach may be more effective to account for shoe deformation during MMH or potentially other types of physical activity.
PMCID: PMC4208210  PMID: 25222032
in-shoe pressure measurement; center of pressure; manual material handling
24.  Muon radiography and deformation analysis of the lava dome formed by the 1944 eruption of Usu, Hokkaido —Contact between high-energy physics and volcano physics— 
Lava domes are one of the conspicuous topographic features on volcanoes. The subsurface structure of the lava dome is important to discuss its formation mechanism. In the 1944 eruption of Volcano Usu, Hokkaido, a new lava dome was formed at its eastern foot. After the completion of the lava dome, various geophysical methods were applied to the dome to study its subsurface structure, but resulted in a rather ambiguous conclusion. Recently, from the results of the levelings, which were repeated during the eruption, “pseudo growth curves” of the lava dome were obtained. The curves suggest that the lava dome has a bulbous shape. In the present work, muon radiography, which previously proved effective in imaging the internal structure of Volcano Asama, has been applied to the Usu lava dome. The muon radiography measures the distribution of the “density length” of volcanic bodies when detectors are arranged properly. The result obtained is consistent with the model deduced from the pseudo growth curves. The measurement appears to afford useful method to clarify the subsurface structure of volcanoes and its temporal changes, and in its turn to discuss volcanic processes. This is a point of contact between high-energy physics and volcano physics.
PMCID: PMC2805507  PMID: 18941290
muon radiography; structure of lava dome; deformation analysis
25.  Neural Correlates of Central Inhibition during Physical Fatigue 
PLoS ONE  2013;8(7):e70949.
Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.
PMCID: PMC3724771  PMID: 23923034

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