Variation in accumulated dose of volumetric-modulated arc therapy for pancreatic cancer due to different beam starting phases.

PURPOSE: To assess the effects of different beam starting phases on dosimetric variations in the clinical target volume (CTV) and organs at risk (OARs), and to identify the relationship between plan complexity and the dosimetric impact of interplay effects in volumetric-modulated arc therapy (VMAT) plans for pancreatic cancer. METHODS: Single and double full-arc VMAT plans were generated for 11 patients. A dose of 50.4 Gy in 28 fractions was prescribed to cover 50% of the planning target volume. Patient-specific Digital Imaging and Communications in Medicine-Radiation Therapy plan files were divided into 10 files based on the respiratory phases in four-dimensional computed tomography (4DCT) simulations. The phase-divided VMAT plans were calculated in consideration of the beam starting phase for each arc and were then combined in the mid-ventilation phase of 4DCT (4D plans). The dose-volumetric parameters were compared with the calculated dose distributions without consideration of the interplay effects (3D plans). Additionally, relationships among plan parameters such as modulation complexity scores, monitor units (MUs), and dose-volumetric parameters were evaluated. RESULTS: Dosimetric differences in the median values associated with different beam starting phases were within ± 1.0% and ± 0.2% for the CTV and ± 0.5% and ± 0.9% for the OARs during single and double full-arc VMAT, respectively. Significant differences caused by variations in the beam starting phases were observed only for the dose-volumetric parameters of the CTV during single full-arc VMAT (P < 0.05), associated with moderate or strong correlations between the MUs and the dosimetric differences between the 4D and 3D plans. CONCLUSIONS: The beam starting phase affected CTV dosimetric variations of single full-arc VMAT. The use of double full-arc VMAT mitigated this problem. However, variation in the dose delivered to OARs was not dependent on the beam starting phase, even for single full-arc VMAT.

Detection of early neuronal damage in CADASIL patients by q-space MR imaging.

INTRODUCTION: q-Space imaging is a novel magnetic resonance (MR) technique that enables the assessment of ultrastructural changes of white matter. We hypothesized that this technique would facilitate the assessment of the progressive nature of neuronal damage seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: This study was approved by the institutional review board. Seven consecutive adult patients (five men and two women) with the CADASIL gene mutation were studied. Two patients were preclinical cases without overt episodes of stroke. The control group consisted of five normal volunteers. All MR examinations were performed using a 1.5-T whole-body imager. q-Space imaging was performed using a single-shot, echo-planar imaging technique and Δ/δ = 142/17 ms. Gradient magnitudes were increased in nine steps to reach a maximal b value of 10,000 s/mm². Total acquisition time of q-space imaging was 25 min. The ADC maps calculated from the b = 1,000 images were used for comparisons. RESULTS: Both q-space imaging and ADC maps depicted progressive neuronal damage. Early neuronal damage was especially well depicted using q-space imaging, with preferential involvement of the frontal lobes and central gray matters. Later progression was better depicted by b = 1,000 ADC maps at the temporal lobes. Visual assessment of images revealed a trend for occipital lobe sparing, especially on q-space imaging. CONCLUSION: q-Space imaging demonstrated early neuronal damage in a characteristic distribution. Since this method appears to be sensitive to early neuronal damage, it could conceivably aid in monitoring patients in the preclinical stage and may help in assessing the effects of future medical interventions.

Individual identification of inbred medaka based on characteristic melanophore spot patterns on the head.

With disease progression, individual differences appear, even in an animal disease model with genetic homogeneity. Therefore, non-invasive long term observation and individual identification is desirable for late-onset diseases. To this end, the natural markings used in ecological studies are preferable to the external invasive markings used in animal husbandry and fisheries management. Here, we propose using the distribution pattern of melanophore spots on the head of an inbred strain of medaka, a small fish model organism with monotonous pigmentation, as biometric identifier. Long term and variation analyses show different patterns whose characteristics can be attributed to individual animals. These findings were also valid in a non-inbred medaka strain and will help individual follow-up of late-onset disease medaka models for the elucidation of the pathogenesis and drug discovery.

Calculation methods for ventricular diffusion-weighted imaging thermometry: phantom and volunteer studies.

A method for the measurement of temperature in the lateral ventricle using diffusion-weighted imaging (DWI) has been proposed recently. This method uses predetermined arbitrary thresholds, but a more objective method of calculation would be useful. We therefore compared four different calculation methods, two of which were newly created and did not require predetermined thresholds. A rectangular polyethylene terephthalate bottle (8 × 10 × 28 cm(3)) was filled with heated water (35.0-38.8 °C) and used as a water phantom. The DWI data of 23 healthy subjects (aged 26-75 years; mean ± standard deviation, 50.13 ± 19.1 years) were used for this study. The temperature was calculated using the following equation: T(°C) = 2256.74/ln(4.39221/D) - 273.15, where D is the diffusion coefficient. The mean ventricular temperature was calculated by four methods: two thresholding methods and two histogram curve-fitting methods. As a reference, we used the temperature measured at the tympanic membrane, which is known to be approximately 1 °C lower than the brain temperature. The averaged differences in temperature between mercury thermometry and classical predetermined thresholding methods for the water phantom were 0.10 ± 0.42 and 0.05 ± 0.41 °C, respectively. The histogram curve-fitting methods, however, yielded temperatures a little lower (averaged differences of -0.24 ± 0.32 and -0.14 ± 0.31 °C, respectively) than mercury thermometry. There was very little difference in temperature between tympanic thermometry and classical predetermined thresholding methods (+0.01 and -0.07 °C, respectively). In humans, however, the histogram curve-fitting methods yielded temperatures approximately 1 °C higher (+1.04 °C and +1.36 °C, respectively), suggesting that temperatures measured in this way more closely approximate the true brain temperature. The histogram curve-fitting methods were more objective and better matched the estimated brain temperature than did classical predetermined thresholding methods, although the standard deviation was wider in the former methods.

L/T-type and L/N-type calcium-channel blockers attenuate cardiac sympathetic nerve activity in patients with hypertension.

Sympathetic nerve activity is augmented by calcium-channel blocker treatment as a result of decreased blood pressure. Dihydropyridine calcium-channel blockers are divided into three different types. The purpose of the present study was to investigate whether treatment effects on hemodynamics, cardiac autonomic nerve activity and plasma norepinephrine levels differ among amlodipine (L type), efonidipine (L + T type) and cilnidipine (L + N type). We enrolled 14 hypertensive patients (seven males, seven females, 70 ± 6 years old) undergoing a monotherapy of amlodipine, efonidipine or cilnidipine into this prospective, open-labeled, randomized, crossover study. At baseline and every 6 months of the treatment period, we repeated the evaluation of hemodynamics, spectral analysis of heart rate variability and plasma norepinephrine levels. Blood pressure and pulse rate were comparable among the three treatments. The low-frequency (LF)/high-frequency (HF) power ratio, an index of cardiac sympathovagal balance, was significantly lower with efonidipine and cilnidipine than with amlodipine, while the HF/total power ratio, an index of cardiac vagal activity, revealed the opposite results. There was no significant correlation between the LF/HF ratio and plasma norepinephrine levels. Antihypertensive monotherapy with efonidipine or cilnidipine attenuates cardiac sympathetic nerve activity more effectively than amlodipine monotherapy.

Age-dependent brain temperature decline assessed by diffusion-weighted imaging thermometry.

Brain metabolism declines with age, but cerebral blood flow (CBF) is less age dependent. We therefore hypothesized that the brain temperature would decline with age, and measured the temperatures of the lateral ventricles in healthy volunteers. Diffusion-weighted imaging (DWI) data from 45 healthy volunteers [mean (± standard deviation) age, 30.6 ± 8.66 years; range, 19-56 years] were used for this study. The temperature of water molecules is directly related to the diffusion coefficient, so that the temperature of cerebrospinal fluid can be measured using DWI. Temperature was calculated using the equation, T ( °C) = 2256.74/ln(4.39221/D) - 273.15, where D is the diffusion coefficient. The lateral ventricles were manually extracted by an experienced neuroradiologist on b(0) images. The mean ventricular temperature was determined from the distribution function of the temperature of all selected voxels. The mean lateral ventricular temperature in healthy volunteers showed a linear decrease with age (correlation coefficient R(2) = 0.8879; p < 0.01), presumably caused by an asynchronous decline in brain metabolism and CBF. DWI-based thermometry demonstrates that ventricular temperature declines with the normal aging process. Further study is warranted to define the relationships between temperature, metabolism and circulation.

Generative image transformer (GIT): unsupervised continuous image generative and transformable model for [123I]FP-CIT SPECT images.

OBJECTIVE: Recently, generative adversarial networks began to be actively studied in the field of medical imaging. These models are used for augmenting the variation of images to improve the accuracy of computer-aided diagnosis. In this paper, we propose an alternative new image generative model based on transformer decoder blocks and verify the performance of our model in generating SPECT images that have characteristics of Parkinson's disease patients. METHODS: Firstly, we proposed a new model architecture that is based on a transformer decoder block and is extended to generate slice images. From few superior slices of 3D volume, our model generates the rest of the inferior slices sequentially. Our model was trained by using [123I]FP-CIT SPECT images of Parkinson's disease patients that originated from the Parkinson's Progression Marker Initiative database. Pixel values of SPECT images were normalized by the specific/nonspecific binding ratio (SNBR). After training the model, we generated [123I]FP-CIT SPECT images. The transformation of images of the healthy control case SPECT images into PD-like images was also performed. Generated images were visually inspected and evaluated using the mean absolute value and asymmetric index. RESULTS: Our model was successfully generated and transformed into PD-like SPECT images. The mean absolute SNBR was mostly less than 0.15 in absolute value. The variation of the obtained dataset images was confirmed by the analysis of the asymmetric index. CONCLUSIONS: These results showed the potential ability of our new generative approach for SPECT images that the generative model based on the transformer realized both generation and transformation by a single model.

Positional repeatability and variation in internal and external markers during volumetric-modulated arc therapy under end-exhalation breath-hold conditions for pancreatic cancer patients.

The purpose of this study was to assess the positional repeatability of internal and external markers among multiple breath-hold (BH) sessions and evaluate the positional variation of these markers within BH sessions for volumetric-modulated arc therapy (VMAT) for pancreatic cancer patients. A total of 13 consecutive pancreatic cancer patients with an internal marker were enrolled. Single full-arc coplanar VMAT was delivered under end-exhalation BH conditions while monitoring the internal marker with kilovoltage (kV) X-ray fluoroscopy. Positional repeatability of the internal and external markers was determined by the difference between the reference and zero position in all BH sessions, and positional variation was defined by the displacement from the reference position in each BH session during megavolt beam delivery. The overall positional repeatability was 0.6 ± 1.5 mm in the X-axis for the centroid of the internal marker (CoIM), -0.1 ± 2.2 mm in the Y-axis for the CoIM, and 0.8 ± 2.2 mm for the external marker. The frequency of an internal marker position appearing > 2 mm from the reference position in the Y-axis, despite the external marker position being ≤2 mm from the reference position, ranged from 0.0 to 39.9% for each patient. Meanwhile, the proportion of sessions with positional variation ≤2 mm was 93.2 and 98.7% for the CoIM and external marker, respectively. External marker motion can be used as a surrogate for pancreatic tumor motion during BH-VMAT delivery; however, margins of ~5 mm were required to ensure positional repeatability.

In vivo Magnetic Resonance Microscopy and Hypothermic Anaesthesia of a Disease Model in Medaka.

In medical and pharmacological research, various human disease models in small fish, such as medaka (Oryzias latipes), have been created. To investigate these disease models noninvasively, magnetic resonance imaging (MRI) is suitable because these small fish are no longer transparent as adults. However, their small body size requires a high spatial resolution, and a water pool should be avoided to maximize the strength of MRI. We developed in vivo magnetic resonance microscopy (MR microscopy) without a water pool by combining hypothermic anaesthesia and a 14.1 T MR microscope. Using in vivo MR microscopy, we noninvasively evaluated the hepatic steatosis level of a non-alcoholic fatty liver disease model in medaka and followed the individual disease progression. The steatosis level was quantified by the MRI-estimated proton density fat-fraction (MRI-PDFF), which estimates the triglyceride fat concentration in liver tissue and is recognized as an imaging biomarker. The MRI-PDFF results agreed with a histological analysis. Moreover, we optimized the hypothermic anaesthesia procedure to obtain a recovery proportion of 1 in the experiment involving MR microscopy. Recovered medaka could not be distinguished from naïve medaka after the experiment. Therefore, the in vivo MR microscopy will expand the possibilities of a human disease model in fish.

Effects of densely sampled dipole field on quantitative susceptibility mapping.

We present a method of resolving a fine structure in a magnetic susceptibility map, which cannot be distinguished by the conventional method, by using a densely sampled dipole field and by expanding a magnetic field perturbation map. We investigate effects of a sampling density of the dipole field on the spatial resolution and on obtained susceptibility values. When the sampling density is increased, a shape of an otherwise undistinguishable fine structure recovers gradually in an obtained susceptibility map. Furthermore, a peak susceptibility value of the fine structure is slowly getting closer to the correct values.

Automated temperature calculation method for DWI-thermometry: the usefulness of LV probability map on healthy subjects.

Diffusion-weight imaging (DWI) has already been incorporated as a regular sequence for patients. If DWI could indicate brain temperature without a complicated procedure, such information may greatly contribute to initial diagnosis. The temperature (T: °C) was calculated using the following equation form the diffusion coefficient (D): T= 2256.74/ln (4.39221/D) - 273.15. The cerebrospinal fluid region for automated temperature computation was segmented by lateral ventricle probability map which was constructed from 46 healthy volunteers. No significant differences were seen between temperatures using the proposed method and the manually segmented. The proposed method of fully automated deep brain temperature computation from DWI may prove feasible for application in MRI consoles.

Effective digitized spatial size of unit dipole field in Quantitative Susceptibility Mapping.

Quantitative Susceptibility Mapping (QSM) calculates a distribution of tissue magnetic susceptibility difference in vivo using measured magnetic field perturbation. The magnetic field perturbation can be approximated in first order by convolution of the susceptibility distribution with a spatial unit dipole field. Since the convolution has to be done in all space, a novel technique using harmonic properties of the dipole field is introduced to confine the calculation within the measurable region. However, discretized dipole field does not satisfy the harmonic property near its orign. Here, we investigate an effective spatial size of the dipole field in relation with the nonharmonic property using Shepp-Logan phantoms including partial volume effects. This study suggests that the dipole field can be effectively restricted to 15 voxels in diameter and that this value relates with the nonharmonic region of the discretized dipole field. Moreover, the effective size in a real space is scaled with a spatial resolution of a QSM experiment.

DWI based thermometry: the effects of b-values, resolutions, signal-to-noise ratio, and magnet strength.

Among MR methods, the most clinically applicable temperature measurement method at deep brain might be the diffusion-weighted image (DWI) thermometry. Although only applicable to cerebrospinal fluid (CSF), it is thought to be potentially useful in assessing the thermal pathophysiology of the brain in both patients and healthy subjects. The purpose of this study was to investigate the effects of b-value, pixel resolution, magnet strength and signal to noise ratio (SNR) for the DWI-thermometry with healthy volunteer. Formerly, an ADC from b=0 and b=1000 has been thought to be useful for diffusion thermometry, this study revealed b=200 to 800 was more appropriate for DWI thermometry. The SNR was strongly affected the results of DWI thermometry.

Moyamoya patients exhibit higher brain temperatures than normal controls.

The balance between heat production (metabolism) and heat removal (blood flow) helps in keeping the temperature of the brain constant. In patients with moyamoya disease, this balance may be disturbed. The purpose of this study was to assess the thermal pathophysiology of the brain in patients with moyamoya disease. The study included 12 consecutive patients with moyamoya disease and 10 controls. Temperature was measured by image postprocessing of diffusion-weighted images. Our noninvasive thermometry showed that the ventricular temperature of moyamoya disease patients was higher than that of normal controls. The mean temperature difference of 1.1 degrees C between the two groups was significant. Patients with moyamoya disease tend to have elevated ventricular temperatures, which may represent a mismatch between cerebral metabolism and perfusion.