Preliminary Imaging Research Articles

Resolution of a Gen-2 handheld optical imager: diffuse and fluorescence imaging studies

A generation-2 (Gen-2) handheld optical imager capable of two-dimensional surface and three-dimensional tomographic imaging has recently been developed. Herein, the ability of the handheld imager to detect and resolve two targets under diffuse and fluorescence imaging conditions has been demonstrated via tissue phantom studies. Two-dimensional surface imaging studies demonstrated that two 0.96 cm diameter Indocyannine Green targets were detected and resolved ~0.5 cm apart (between edges) at a target depth of 1 cm during diffuse imaging and up to 2 cm depth during fluorescence imaging. Preliminary 3D tomographic imaging capability to resolve the two targets was also demonstrated, but requires extensive future studies.

Clinical Trial of an Innovative Dual-Processing Group Therapy Relapse Prevention Protocol Conducted in a Community-Based Setting

The purpose of this article is to describe an interdisciplinary clinical trial conducted in a community-based setting. The article will (a) present an overview of the current study, (b) detail an innovative outpatient relapse prevention group therapy practice model informed by the neuroscientific literature on addiction, (c) present case examples of patient response to treatment, and (d) provide qualitative data of patient feedback and preliminary functional magnetic resonance imaging data results.

Imaging: What can it tell us about parkinsonian gait?

Functional neuroimaging has provided new tools to study cerebral gait control in Parkinson's disease (PD). First, imaging of blood flow functions has identified a supraspinal locomotor network that includes the (frontal) cortex, basal ganglia, brainstem tegmentum, and cerebellum. These studies also emphasize the cognitive and attentional dependency of gait in PD. Furthermore, gait in PD and related syndromes like progressive supranuclear palsy may be associated with dysfunction of the indirect, modulatory prefrontal-subthalamic-pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar input appears to be preserved and may contribute to the unflexible gait pattern in parkinsonian gait. Second, neurotransmitter and proteinopathy imaging studies are beginning to unravel novel mechanisms of parkinsonian gait and postural disturbances. Dopamine displacement imaging studies have shown evidence for a mesofrontal dopaminergic shift from a depleted striatum in parkinsonian gait. This may place additional burden on other brain systems mediating attention functions to perform previously automatic motor tasks. For example, our preliminary cholinergic imaging studies suggest significant slowing of gait speed when additional forebrain cholinergic denervation occurs in PD. Cholinergic denervation of the pedunculopontine nucleus and its thalamic projections have been associated with falls and impaired postural control. Deposition of β-amyloid may represent another non-dopaminergic correlate of gait disturbance in PD. These findings illustrate the emergence of dopamine non-responsive gait problems to reflect the transition from a predominantly hypodopaminergic disorder to a multisystem neurodegenerative disorder involving non-dopaminergic locomotor network structures and pathologies.

Whole‐spine Magnetic Resonance Imaging Study in Healthy Chinese Adolescents

To establish a preliminary magnetic resonance imaging (MRI) database of whole spine of healthy Chinese adolescents. MRI examination of whole spine and hindbrain was performed in 41 enrolled students aged 11-17 years (mean age 13.95; 18 males, 23 females) using a 1.5-T MR Scanner. Measurements of the ratio of anteroposterior (AP) and transverse (TS) diameters of the cord, cerebellar tonsillar level related to the basion-opsithion (BO) line, location of conus medullaris, total cord length, total vertebral length, cord/vertebral length ratio, thoracic cord area, thoracic vertebral area, thoracic cord/vertebral area ratio were obtained. Mean values of cervical AP and TS were 6.63 mm and 12.21 mm, respectively. The mean level of cerebellar tonsillar related to BO line was 3.97 mm. Mean level of conus medullaris located in L1 lower 1/3. Total cord length was 399.34 mm, total vertebral length was 529.49 mm, Cord/vertebral length ratio was 0.75 and thoracic cord/vertebral area ratio was 0.17 on average. Vertebral length was correlated with age (r = 0.352, P = 0.024) whereas cord length and their ratio were not (P > 0.05). Compared with female, male had significantly larger cervical AP and TS, longer cervical cord (P < 0.01), higher position of conus medullaris (P < 0.05). MRI is a useful tool for assessment of the whole spine. The longitudinal and cross-sectional morphology of spinal cord in healthy Chinese adolescents may benefit further study of spine cord in adolescent idiopathic scoliosis as well as in other spine diseases.

Development of a simple pressure and heat stimulator for intra- and interdigit functional magnetic resonance imaging

For this study, we developed a simple pressure and heat stimulator that can quantitatively control pressure and provide heat stimulation to intra- and interdigit areas. The developed stimulator consists of a control unit, drive units, and tactors. The control unit controls the stimulation parameters, such as stimulation types, intensity, time, and channel, and transmits a created signal of stimulation to the drive units. The drive units operate pressure and heat tactors in response to commands from the control unit. The pressure and heat tactors can display various stimulation intensities quantitatively, apply stimulation continuously, and adjust the stimulation areas. Additionally, they can easily be attached to and detached from the digits. The developed pressure and heat stimulator is small in total size, easy to install, and inexpensive to manufacture. The new stimulator operated stably in a magnetic resonance imaging (MRI) environment without affecting the obtained images. A preliminary functional magnetic resonance imaging (fMRI) experiment confirmed that differences in activation of somatosensory areas were induced from the pressure and heat stimulation. The developed pressure and heat stimulator is expected to be utilized for future intra- and interdigit fMRI studies on pressure and heat stimulation.

Brown adipose tissue mapping in rats with combined intermolecular double‐quantum coherence and Dixon water–fat MRI

Brown adipose tissue (BAT) is a promising therapeutic target in obesity studies. Recently, MRI has been proposed for the mapping of BAT. However, because of the limitation of spatial resolution, similar to the existing positron emission tomography and computed tomography techniques for BAT detection, it fails to distinguish BAT cells when they are mixed with other cells. In this work, a new MRI method is proposed, combining intermolecular double-quantum coherence and the chemical shift-encoded Dixon method. Its contrast depends on the water to fat ratio at the cellular scale, which is smaller than the imaging voxel size. The feasibility of this MRI method was shown with computer simulations and phantoms, and preliminary imaging of BAT of rats at 7 T. Both computer simulations and experimental results are consistent with theoretical predictions. The method provides a novel contrast mechanism and can map BAT distribution exclusively. In particular, a mixture of BAT cells and white adipose tissue cells was detected in an older rat, which was undetectable by other noninvasive methods. This method may be applicable to a wide range of uses in BAT-related studies, including the formation and variation of BAT.

New device based on the super spatial resolution (SSR) method

Recently it have been described that innovative methods, namely Super Spatial Resolution (SSR), can be used to improve the scintigraphic imaging. The aim of SSR techniques is the enhancement of the resolution of an imaging system, using information from several images. In this paper we describe a new experimental apparatus that could be used for molecular imaging and small animal imaging. In fact we present a new device, completely automated, that uses the SSR method and provides images with better spatial resolution in comparison to the original resolution. Preliminary small animal imaging studies confirm the feasibility of a very high resolution system in scintigraphic imaging and the possibility to have gamma cameras using the SSR method, to perform the applications on functional imaging.

Kit-like 18F-labeling of RGD-19F-Arytrifluroborate in high yield and at extraordinarily high specific activity with preliminary in vivo tumor imaging

Positron Emission Tomography (PET) is a rapidly expanding, cutting edge technology for preclinical evaluation, cancer diagnosis and staging, and patient management. A one-step aqueous (18)F-labeling method, which can be applied to peptides to provide functional in vivo images, has been a long-standing challenge in PET imaging. Over the past few years, we have sought a rapid and mild radiolabeling method based on the aqueous radiosynthesis of in vivo stable aryltrifluoroborate (ArBF(3)(-)) conjugates. Recent access to production levels of (18)F-Fluoride led to a fluorescent-(18)F-ArBF(3)(-) at unprecedentedly high specific activities of 15Ci/μmol. However, extending this method to labeling peptides as imaging agents has not been explored. In order to extend these results to a peptide of clinical interest in the context of production-level radiosynthesis, we applied this new technology for labeling RGD, measured its specific activity by standard curve analysis, and carried out a preliminary evaluation of its imaging properties. RGD was labeled in excellent radiochemical yields at exceptionally high specific activity (~14Ci/μmol) (n = 3). Preliminary tumor-specific images corroborated by ex vivo biodistribution data with blocking controls show statistically significant albeit relatively low tumor uptake along with reasonably high tumor:blood ratios (n = 3). Isotope exchange on a clinically useful (18)F-ArBF(3)(-) radiotracer leads to excellent radiochemical yields and exceptionally high specific activities while the anionic nature of the aryltrifluoroborate prosthetic results in very rapid clearance. Since rapid clearance of the radioactive tracer is generally desirable for tracer development, these results suggest new directions for varying linker arm composition to slightly retard clearance rather than enhancing it. This work is the first to use production levels of (18)F-activity to directly label RGD at specific activities that are an order of magnitude higher than most reports and thereby increases the distribution window for radiotracer production and delivery.

PII: S1525-5050(12)00697-X

Most murine and rodent epilepsy syndromes provide models for absence epilepsies. The baboon, on the other hand, not only provides a model of photosensitive generalized epilepsy but closely resembles a common form of idiopathic generalized epilepsy, namely juvenile myoclonic epilepsy (JME). Baboons, regardless of subspecies, exhibit rare spontaneous generalized seizures: myoclonic and generalized tonic-clonic seizures; the seizures present in adolescence occurring with morning predominance. In addition to intermittent light stimulation (ILS), seizures can be triggered by stress and handling as well as by proconvulsant medications. Absence seizures also occur, but they are less prevalent in baboons than in people with JME. On scalp EEG, interictal epileptic discharges are commonly generalized spike-and-wave discharges of 4- to 6-Hz frequency, rarely 2- to 3-Hz frequency. These can be activated by sleep and medications, including low-dose ketamine. The prevalence of photosensitivity in baboons is 38%, which is similar to its prevalence in human JME. Antiepileptic medications have mainly been tested with respect to reduction of ictal or interictal discharges provoked by ILS, with similar AED profiles proved to be efficacious in suppressing photoparoxysmal and convulsive responses as generalized seizures in JME. As a potential model for JME, the baboon provides the opportunity to correlate functional and structural neuroimaging findings with invasive electrophysiology and histopathology. This presentation reviews preliminary imaging, intracranial EEG and histopathological data recently acquired in this animal model by our laboratory, and discusses the potential relevance to mechanisms underlying JME.

SU-E-T-292: In-Vivo Blood Oxygen Measurements Via Interstitial Fiber Optic Probe and Photoacoustic Imaging

Purpose: Better understanding of hemodynamics and oxygen transport in response to radiation will enable clinicians to optimize radiotherapy treatment regimens. It is well‐known that oxygenated tissue is significantly more responsive to damage caused by irradiation. We sought to explore the real‐time hemodynamics and blood oxygenation dynamics in response to radiation using a novel interstitial fiber‐optic probe and a photoacoustic imaging system. Methods: Mice bearing xenografted tumors composed of a head and neck cancer cell line (UM‐SCC47) and a patient‐derived xenograft (UW‐SCC36) were irradiated (10 Gy). Blood oxygena saturation (S) and blood volume fraction (B) were monitored in real time using an interstitial fiber optic probe as well as a photoacoustic imaging system (using a 21 MHz transducer, and infra red wavelengths of 750 and 850nm on the Vevo LAZR (R)). Results: A significant drop in blood oxygen saturation was found within 15 minutes following irradiation using the interstitial fiber optic probe. Meanwhile, Blood volume fraction remained constant. Preliminary photoacoustic imaging provided evaluation of the spatial characteristics of blood‐oxygen dynamics and showed qualitative agreement with probe measurements. The measurements were compared to gain a better understanding of the fiber optic probe's spatial averaging, also. Conclusion: While development of the interstitial fiber optic probe continues, it appears to provide real‐time assessment of blood‐oxygen dynamics. Correlation of optimal reoxygenation with split dose radiation response is ongoing and may provide insight that could lead to improvements in the delivery of radiation therapy. This is particularly valuable for hypofractionated treatments as this information can guide the timing, size, and number of fractions for radiotherapy treatments. Minalini Lakshman is an employee of the VisualSonics company; however, the company did not provide any financial support for this work.

Implementation of LYSO/PSPMT Block Detector With All Digital DAQ System

We are developing, at the Huazhong University of Science and Technology, a small-animal positron emission tomograph (PET) scanner that has two new features. Firstly, it uses detector modules that are based on a new digital readout electronics previously investigated and reported by us. Secondly, it can arrange the detector modules into various scanner geometries for different imaging needs. In this paper, we will describe the design and implementation of the detector module and report its performance properties. The detector module has a total detection sensitive area of 5.3 × 5.3 cm2, an overall energy resolution of 14.1% FWHM at 511 keV, and a block-level coincidence timing resolution of 1.5 ns FWHM. In addition, our preliminary imaging study shows that our small-animal PET scanner can resolve 1.0 mm-diameter rods separated by 2.0 mm.

Comparison of high-resolution MRI with CT angiography and digital subtraction angiography for the evaluation of middle cerebral artery atherosclerotic steno-occlusive disease

Intracranial atherosclerotic disease is increasingly recognized as a major stroke subtype worldwide. Current diagnostic evaluation of atherosclerotic disease of the middle cerebral artery (MCA) relies on detection of stenoses with luminographic imaging studies that do not directly visualize plaque unlike high-resolution MRI. This retrospective study seeks to evaluate the accuracy of high-resolution MRI vessel wall imaging, computed tomographic angiography (CTA) and digital subtraction angiography (DSA) in measuring the degree of stenosis within the MCA. 28 recently symptomatic patients with MCA territory symptoms underwent preliminary imaging with CTA followed by high-resolution MRI at 3-Tesla and definitive imaging with DSA for detection of M1 territory steno-occlusive lesions. Measurements of MCA segments on MRI and CTA were compared with reference to DSA values. Sensitivity and specificity of high-resolution MRI vessel wall imaging, CTA using maximum intensity projection (MIP) and CTA using volume rendering (VR) for the detection of stenosis > 50 % and occlusion were 80.0 and 53.6 %, 72.2 and 72.7 %, and 77.8 and 18.2 %, respectively. MRI-derived values correlated better with DSA (Spearman R = 0.68, p < 0.01) than CTA MIP and VR (Spearman R = 0.45, 0.22; p = 0.02, 0.24, respectively). High-resolution MRI of the MCA is capable of accurately measuring the degree of stenosis and is more sensitive than CTA in a sample of high-risk, symptomatic patients. This study, combined with previous reports, supports the potential of morphological MRI to measure intracranial atherosclerotic plaque non-invasively.

White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

Multiphase post-mortem computed tomography angiography in seven lethal cases of great height falls: Preliminary results of a French experience

Background The use of enhanced multislice computed tomography (MSCT) in forensic sciences has been recently developed in order to improve radiological vascular and organs injuries detection. Methods Seven suicidal cases of great height falls (4 women, and 3 men) underwent a multiphase post-mortem computed tomography angiography (MPMCTA) before medico-legal autopsy. The estimated height falls varied from 5 to 15 m. All corpses were prepared with a surgical cannulation of femoral vessels. After a non-MSCT exploration, a controlled perfusion device (Virtangio ® machine) was used with paraffin oil mixed with specific contrast agent (Angiofil ® ), allowing three time-different acquisitions (arterial, venous, dynamic). Two radiologists proceeded to images analysis. The forensic pathologist undergoing autopsies knew preliminary imaging results. Results The results of MPMCTA explorations and autopsies differed concerning detection of gas, bone fractures, and vascular ruptures (mainly cerebral), with a superiority of the MPMCTA. Autopsies were superior to MPMCTA for detection of some superficial skin lesions, which were easily accessible to external examination. Discussion Both techniques were able to diagnose some classical and typical bone, visceral and vascular lesions. Additionally, some rare injuries were found like coronary desinsertion, double thoracic aortic ruptures, inferior vena cava laceration extended to the right atrium, and pulmonary vein disruption. These findings were found with both techniques, but MPMCTA permitted better in situ lesions' illustration and documentation. Furthermore, realization of different-time acquisitions was essential for detection and comprehension of abnormal traumatic communication between cardiac cavities. Conclusion This study illustrates the complementarity of MPMCTA and autopsy in traumatic cases, and especially for cases of lethal great height falls.

In-line X-ray lensless imaging with lithium fluoride film detectors

In this work, we present preliminary in-line X-ray lensless projection imaging results at a synchrotron facility by using novel solid-state detectors based on non-destructive readout of photoluminescent colour centres in lithium fluoride thin films. The peculiarities of LiF radiation detectors are high spatial resolution on a large field of view, wide dynamic range, versatility and simplicity of use. These properties offered the opportunity to test a broadband X-ray synchrotron source for lensless projection imaging experiments at the TopoTomo beamline of the ANKA synchrotron facility by using a white beam spectrum (3–40 keV). Edge-enhancement effects were observed for the first time on a test object; they are discussed and compared with simulations, on the basis of the colour centre photoluminescence linear response found in the investigated irradiation conditions.

Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: A preliminary quantitative imaging study

While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods. CR monkeys expressed significantly lower levels (∼30% on average) of GFAP than Controls in the CA region of the hippocampus and entorhinal cortex, suggesting a protective effect of CR in limiting astrogliosis. These results recapitulate the neuroprotective effects of CR seen in shorter-lived animal models. There was a significant positive association between age and average amyloid plaque pathology in these animals, but there was no significant difference in amyloid plaque distribution between the two groups. Two of the seven Control animals (28.6%) and one of the six CR animal (16.7%) did not express any amyloid plaques, five of seven Controls (71.4%) and four of six CR animals (66.7%) expressed minimal to moderate amyloid pathology, and one of six CR animals (16.7%) expressed severe amyloid pathology. That CR affects levels of GFAP expression but not amyloid plaque load provides some insight into the means by which CR is beneficial at the microstructural level, potentially by offsetting the increased load of oxidatively damaged proteins, in this non-human primate model of aging. The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms.

Fluorescent x-ray computed tomography using the pinhole effect for biomedical applications

We propose a fluorescent x-ray computed tomography using volumetric beam and pinhole collimator to obtain 3-dimensional image effectively, aimed at providing molecular imaging with quantifiable measures and sub-millimeter spatial resolution. In this study, we demonstrate the feasibility of this concept and investigate imaging properties such as spatial resolution, contrast resolution and quantifiable measures, by imaging physical phantoms. A preliminary imaging system using monochromatic synchrotron x-rays was constructed at the BLNE-7A bending-magnet beamline (6.5GeV) at KEK, Japan.

Imaging Bolometers for Visualization of Plasma Radiation and Cross-Validation of Three Dimensional Impurity Transport Models for the Large Helical Device

The InfraRed imaging Video Bolometer (IRVB) measures the radiation from the plasma in two dimensions, giving an image of the plasma radiation power loss. Using a geometry matrix calculated from a model of the LHD first wall, the IRVB sightline geometry and a three dimensional (3D) plasma grid, a synthetic instrument is developed using the 3D carbon impurity radiation results of the EMC3-EIRENE edge impurity transport code as an input. The output of the synthetic instrument are images of the plasma radiation at the IRVB foil due to the EMC3-EIRENE code, which are qualitatively compared with preliminary experimental images from the IRVB. Such a comparison for detached discharges in LHD in which an externally induced m/n = 1/1 magnetic island is applied shows that when the magnetic island is moved 36 degrees toroidally the enhanced radiation in the x-points of the magnetic island also moves as predicted by the EMC3-EIRENE code.

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

BackgroundThe significant progress in nanotechnology provides a wide spectrum of nanosized material for various applications, including tumor targeting and molecular imaging. The aim of this study was to evaluate multifunctional liposomal nanoparticles for targeting approaches and detection of tumors using different imaging modalities. The concept of dual-targeting was tested in vitro and in vivo using liposomes derivatized with an arginine-glycine-aspartic acid (RGD) peptide binding to αvβ3 integrin receptors and a substance P peptide binding to neurokinin-1 receptors.MethodsFor liposome preparation, lipids, polyethylene glycol building blocks, DTPA-derivatized lipids for radiolabeling, lipid-based RGD and substance P building blocks and imaging labels were combined in defined molar ratios. Liposomes were characterized by photon correlation spectroscopy and zeta potential measurements, and in vitro binding properties were tested using fluorescence microscopy. Standardized protocols for radiolabeling were developed to perform biodistribution and micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies in nude mice bearing glioblastoma and/or melanoma tumor xenografts. Additionally, an initial magnetic resonance imaging study was performed.ResultsLiposomes were radiolabeled with high radiochemical yields. Fluorescence microscopy showed specific cellular interactions with RGD-liposomes and substance P-liposomes. Biodistribution and micro-SPECT/CT imaging of 111In-labeled liposomal nanoparticles revealed low tumor uptake, but in a preliminary magnetic resonance imaging study with a single-targeted RGD-liposome, uptake in the tumor xenografts could be visualized.ConclusionThe present study shows the potential of liposomes as multifunctional targeted vehicles for imaging of tumors combining radioactive, fluorescent, and magnetic resonance signaling. Specific in vitro tumor targeting by fluorescence microscopy and radioactivity was achieved. However, biodistribution studies in an animal tumor model revealed only moderate tumor uptake and no additive effect using a dual-targeting approach.

High-Speed Optical Coherence Tomography System Using a 200-kHz Swept Light Source with a KTN Deflector

We demonstrate a high-speed swept-source optical coherence tomography (SS-OCT) system, which is based on a high-speed swept light source and a Mach-Zehnder interferometer with a high-speed photodetector. The light source is an external-cavity laser tuned by a KTN electro-optic deflector, which exhibits a very fast response and large deflection. The scanning wavelength range is almost 80 nm up to 200 kHz with a ±400-V deflector driving voltage. The system acquires 1 mm × 1 mm images consisting of 200 × 200 pixels within few milliseconds. We present preliminary SS-OCT images of an in-vitro human nail and an in-vivo finger pad.