Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks.

OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18 F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy. RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness. CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

A simulated car-driving study on the effects of acute administration of levocetirizine, fexofenadine, and diphenhydramine in healthy Japanese volunteers.

OBJECTIVE: Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects. METHODS: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed. RESULTS: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation. CONCLUSIONS: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.

[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease.

PURPOSE: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer. METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks. RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex. CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.

A triple-imaging-modality system for simultaneous measurements of prompt gamma photons, prompt x-rays, and induced positrons during proton beam irradiation.

Objective. Prompt gamma photon, prompt x-ray, and induced positron imaging are possible methods for observing a proton beam's shape from outside the subject. However, since these three types of images have not been measured simultaneously nor compared using the same subject, their advantages and disadvantages remain unknown for imaging beam shapes in therapy. To clarify these points, we developed a triple-imaging-modality system to simultaneously measure prompt gamma photons, prompt x-rays, and induced positrons during proton beam irradiation to a phantom.Approach. The developed triple-imaging-modality system consists of a gamma camera, an x-ray camera, and a dual-head positron emission tomography (PET) system. During 80 MeV proton beam irradiation to a polymethyl methacrylate (PMMA) phantom, imaging of prompt gamma photons was conducted by the developed gamma camera from one side of the phantom. Imaging of prompt x-rays was conducted by the developed x-ray camera from the other side. Induced positrons were measured by the developed dual-head PET system set on the upper and lower sides of the phantom.Main results. With the proposed triple-imaging-modality system, we could simultaneously image the prompt gamma photons and prompt x-rays during proton beam irradiation. Induced positron distributions could be measured after the irradiation by the PET system and the gamma camera. Among these imaging modalities, image quality was the best for the induced positrons measured by PET. The estimated ranges were actually similar to those imaged with prompt gamma photons, prompt x-rays and induced positrons measured by PET.Significance. The developed triple-imaging-modality system made possible to simultaneously measure the three different beam images. The system will contribute to increasing the data available for imaging in therapy and will contribute to better estimating the shapes or ranges of proton beam.

Hybrid imaging of prompt x-rays and induced positrons using a pinhole gamma camera during and after irradiation of protons.

Objective. Prompt x-ray imaging using a low-energy x-ray camera is a promising method for observing a proton beam's shape from outside the subject. Furthermore, imaging of positrons produced by nuclear reactions with protons is a possible method for observing the beam shape. However, it has not been possible to measure these two types of images with a single imaging system due to the limited imaging capability of existing systems. Imaging of both prompt x-rays and the distribution of positrons may compensate for the shortcomings of each method.Approach. We conducted imaging of the prompt x-ray using a pinhole x-ray camera during irradiation with protons in list mode. Then, after irradiation with protons, imaging of annihilation radiations from the produced positrons was conducted using the same pinhole x-ray camera in list mode. After this imaging, list-mode data were sorted to obtain prompt x-ray images and positron images.Main results. With the proposed procedure, we could measure both prompt x-ray images and induced positron images with a single irradiation by a proton beam. From the prompt x-ray images, ranges and widths of the proton beams could be estimated. The distributions of positrons were slightly wider than those of the prompt x-rays. From the time sequential positron images, we could derive the time activity curves of the produced positrons.Significance. Hybrid imaging of prompt x-rays and induced positrons using a pinhole x-ray camera was achieved. The proposed procedure would be useful for measuring prompt x-ray images during irradiation to estimate the beam structures as well as for measuring the induced positron images after irradiation to estimate the distributions and time activity curves of the induced positrons.

Proton range monitoring using 13N peak for proton therapy applications.

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications.

A Feasibility Study on Proton Range Monitoring Using 13N Peak in Inhomogeneous Targets.

Proton irradiations are highly sensitive to spatial variations, mainly due to their high linear energy transfer (LET) and densely ionizing nature. In realistic clinical applications, the targets of ionizing radiation are inhomogeneous in terms of geometry and chemical composition (i.e., organs in the human body). One of the main methods for proton range monitoring is to utilize the production of proton induced positron emitting radionuclides; these could be measured precisely with positron emission tomography (PET) systems. One main positron emitting radionuclide that could be used for proton range monitoring and verification was found to be 13N that produces a peak close to the Bragg peak. In the present work, we have employed the Monte Carlo method and Spectral Analysis (SA) technique to investigate the feasibility of utilizing the 13N peak for proton range monitoring and verification in inhomogeneous targets. Two different phantom types, namely, (1) ordinary slab and (2) MIRD anthropomorphic phantoms, were used. We have found that the generated 13N peak in such highly inhomogeneous targets (ordinary slab and human phantom) is close to the actual Bragg peak, when irradiated by incident proton beam. The feasibility of using the SA technique to estimate the distribution of positron emitter was also investigated. The current findings and the developed tools in the present work would be helpful in proton range monitoring and verification in realistic clinical radiation therapy using proton beams.

Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin.

AIMS: The strength of sedation due to antihistamines can be evaluated using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy following oral administration of cetirizine (10 and 20 mg) in order to examine dose dependency. METHODS: Fifteen healthy male volunteers (age range, 20-35 years) were divided into 3 subgroups and were studied following single oral administration of cetirizine at 10 mg (n = 5) and 20 mg (n = 5) or hydroxyzine at 30 mg (n = 5) using PET with 11C-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H(1)RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H(1)RO was examined for each antihistamine. RESULTS: The averaged H(1)ROs of cetirizine 10 mg, 20 mg, and hydroxyzine 30 mg in the prefrontal and cingulate cortices was 12.6%, 25.2%, and 67.6%, respectively. The H(1)RO of hydroxyzine 30 mg correlated well with subjective sleepiness (p < 0.001); however, those of cetirizine 10 and 20 mg showed no correlation with subjective sleepiness. CONCLUSION: It was demonstrated that the brain penetration of orally administered cetirizine was dose-dependent. Cetirizine 10 mg, with its low H(1)RO and thus minimal sedation, could be more safely used than cetirizine 20 mg for the treatment of various allergic disorders.

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study.

OBJECTIVE: Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using (18)F-2-fluoro-2-deoxyglucose ([(18)F]FDG) and three-dimensional positron emission tomography (3-D PET). METHODS: Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O(2) consumption (VO(2max)). [(18)F]FDG was injected 10 min later following the exercise task. Wholebody 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P < 0.05) were determined using Scheffe's test (post hoc analysis). RESULTS: Quantitative analysis demonstrated that rMRGlc increased (P < 0.05) in the skeletal muscles of the thigh at mild or moderate workloads when compared with the resting controls. For visceral organs such as the liver and brain, metabolic reduction was significant (P < 0.05) at mild and/or moderate exercise workload. CONCLUSIONS: The present study demonstrated linear increases or decreases in glucose uptake by skeletal muscles and viscera with mild and moderate exercise workloads, suggesting the presence of homeostatic energy metabolism. This result supports the finding that [(18)F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO(2max)). The results of this investigation may contribute to sports medicine and rehabilitation science.

Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: 'Bepotastine besilate' is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies. However, only a few clinical studies regarding its sedative property are available. In addition, histamine H(1) receptor occupancy (H(1)RO) of this new antihistamine has never been measured by positron emission tomography (PET). WHAT THIS STUDY ADDS: This paper provides the first measurement result of cerebral H(1)RO of bepotastine besilate (approximately 15%) as determined by PET. This result is in accordance with the clinical classification of bepotastine as a second-generation antihistamine. In addition, the relationship between subjective sleepiness and cerebral H(1)RO of this second-generation antihistamine is demonstrated for the first time using a placebo-controlled crossover study design. AIMS Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H(1) receptor occupancy (H(1)RO) in the brain using positron emission tomography (PET). The aim was to measure H(1)RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine. METHODS: Eight healthy male volunteers (mean age +/- SD 24.4 +/- 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with (11)C-doxepin in a crossover study design. Binding potential ratio and H(1)ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H(1)RO was examined. RESULTS: H(1)RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H(1)ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H(1)ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001). CONCLUSION: Oral bepotastine (10 mg), with its relatively low H(1)RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.

Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study.

Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET). Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

Functional brain mapping of actual car-driving using [18F]FDG-PET.

AIMS: This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. METHODS: Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. RESULTS: Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. CONCLUSION: The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease.

UNLABELLED: Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives. METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117. CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

Evaluation of the biodistribution and radiation dosimetry of the 18F-labelled amyloid imaging probe [18F]FACT in humans.

BACKGROUND: The biodistribution and radiation dosimetry of the 18F-labelled amyloid imaging probe ([18F] FACT) was investigated in humans. METHODS: Six healthy subjects (three males and three females) were enrolled in this study. An average of 160.8 MBq of [18F] FACT was intravenously administered, and then a series of whole-body PET scans were performed. Nineteen male and 20 female source organs, and the remainder of the body, were studied to estimate time-integrated activity coefficients. The mean absorbed dose in each target organ and the effective dose were estimated from the time-integrated activity coefficients in the source organs. Biodistribution data from [18F] FACT in mice were also used to estimate absorbed doses and the effective dose in human subjects; this was compared with doses of [18F] FACT estimated from human PET data. RESULTS: The highest mean absorbed doses estimated using human PET data were observed in the gallbladder (333 ± 251 µGy/MBq), liver (77.5 ± 14.5 µGy/MBq), small intestine (33.6 ± 30.7 µGy/MBq), upper large intestine (29.8 ± 15.0 µGy/MBq) and lower large intestine (25.2 ± 12.6 µGy/MBq). The average effective dose estimated from human PET data was 18.6 ± 3.74 µSv/MBq. The highest mean absorbed dose value estimated from the mouse data was observed in the small intestine (38.5 µGy/MBq), liver (25.5 µGy/MBq) and urinary bladder wall (43.1 µGy/MBq). The effective dose estimated from the mouse data was 14.8 µSv/MBq for [18F] FACT. CONCLUSIONS: The estimated effective dose from the human PET data indicated that the [18F] FACT PET study was acceptable for clinical purposes.

[(11)C]Doxepin binding to histamine H1 receptors in living human brain: reproducibility during attentive waking and circadian rhythm.

Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET) enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [(11)C]raclopride and [(11)C]FLB457 revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous [(11)C]raclopride studies, we examined whether the levels of neuronal release of histamine might change [(11)C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test-retest reliability of quantitative measurement of [(11)C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [(11)C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (less than 10%) was not significant. Similarly, the binding potential of [(11)C]doxepin in the cerebral cortex was slightly higher in the morning than that in the afternoon, but it was also insignificant. These data suggest that higher histamine release during wakefulness could not decrease the [(11)C]doxepin binding in the brain. This study confirmed the reproducibility and reliability of [(11)C]doxepin in the previous imaging studies to measure the H1 receptor.

Long-term performance evaluation of positron emission tomography: analysis and proposal of a maintenance protocol for long-term utilization.

OBJECTIVE: Positron emission tomography (PET) scanners require periodic monitoring in order to maintain scanner performance. The aim of the present study was to examine the deterioration of PET scanner performance caused by aging. METHODS: We retrospectively examined PET scanner performance alterations in terms of sensitivity, spatial resolution, false coincidences due to scatter and random coincidences based on 13 years of follow-up data, including data when the PET scanner underwent an overhaul at the 10th year after installation. Sensitivity and scatter fraction were calculated by using cross calibration factor (CCF) measurement data, which are collected routinely. Efficacy of the examining the sensitivity and scatter was confirmed by NEMA measurements. Trans-axial resolution was measured as full width at half-maximum (FWHM) and full width at tenth-maximum (FWTM) at 0-20 cm offset from the field of view (FOV) center at the time of installation, 8 years after installation, and immediately after the overhaul. Random coincidence rate fraction was measured in a wide range of count rates before and after the overhaul. RESULTS AND DISCUSSION: The results indicated that the total reduction of sensitivity during the first 10 years was 41% of the initial value in terms of NEMA measurement, and that the annual reduction of sensitivity progressed at a rate of 4.7% per year in terms of CCF measurement data. The changes in sensitivity can be calculated using CCF measurement data. Regarding the spatial resolution, mean FWHM and FWTM values were increased by 1.7 and 3.6%, respectively, in 8 years after installation. The relative scatter fraction was significantly increased compared with that before the overhaul. The random fraction decreased by 10-15% after the overhaul within a certain range of random count rates (1-120 kcps). In the case of our scanner, the parameter that displayed the largest change was the sensitivity, and this change was thought to be caused by the reduction of photomultiplier tube (PMT) gain, although the changes in PMT gain can cause various types of performance deterioration, as investigated in this study. CONCLUSION: We observed that the sensitivity of our PET scanner generally deteriorated due to aging. Sensitivity monitoring using CCF measurements can be an easy and useful method for monitoring and maintaining the performance of PET scanners against aging. Since the data were obtained from a single scanner, the authors would encourage the initiation of a follow-up study involving various scanners.