• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.490-496
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• 1998

Purpose: We evaluated brain perfusion SPECT findings of MELAS syndrome and mitochondrial myopathy in correlation with MR imaging in search of specific imaging features. Materials and Methods: Subjects were five patients (four females and one male; age range, 1 to 25 year) who presented with repeated stroke-like episodes, seizures or developmental delay or asymptomatic but had elevated lactic acid in CSF and serum. Conventional non-contrast MR imaging and Tc-99m-ethyl cysteinate dimer (ECD) brain perfusion SPECT were Performed and imaging features were analyzed. Results: MRI demonstrated increased T2 signal intensities in the affected areas of gray and white matters mainly in the parietal (4/5) and occipital lobes (4/5) and in the basal ganglia (1/5), which were not restricted to a specific vascular territory. SPECT demonstrated decreased perfusion in the corresponding regions of MRI lesions. In addition, there were perfusion defects in parietal (1 patient), temporal (2), and frontal (1) lobes and basal ganglia (1) and thalami (2). In a patient with mitochondrial myopathy who had normal MRI, decreased perfusion was noted in left parietal area and bilateral thalami. Conclusion: Tc-99m ECD SPECT imaging in patients with MELAS syndrome and mitochondrial myopathy showed hypoperfusion of parieto-occipital cortex, basal ganglia, thalamus and temporal cortex, which were not restricted to a specific vascular territory. There were no specific imaging features on SPECT. The significance of abnormal perfusion on SPECT without corresponding MR abnormalities needs to be evaluated further in larger number of patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.553-564
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• 1998

Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.102-109
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• 2009

Purpose: Flash 3D (pixon(R) method; 3D OSEM) was developed as a software program to shorten exam time and improve image quality through reconstruction, it is an image processing method that usefully be applied to nuclear medicine tomography. If perfoming brain diamox perfusion scan by reconstructing subtracted images by Flash 3D with shortened image acquisition time, there was a problem that SNR of subtracted image is lower than basal image. To increase SNR of subtracted image, we use LEAP collimators, and we emphasized on sensitivity of vessel dilatation than resolution of brain vessel. In this study, our purpose is to confirm possibility of application of LEAP collimators at brain diamox perfusion tomography, identify proper reconstruction factors by using Flash 3D. Materials and methods: (1) The evaluation of phantom: We used Hoffman 3D Brain Phantom with $^{99m}Tc$. We obtained images by LEAP and LEHR collimators (diamox image) and after 6 hours (the half life of $^{99m}Tc$: 6 hours), we use obtained second image (basal image) by same method. Also, we acquired SNR and ratio of white matters/gray matters of each basal image and subtracted image. (2) The evaluation of patient's image: We quantitatively analyzed patients who were examined by LEAP collimators then was classified as a normal group and who were examined by LEHR collimators then was classified as a normal group from 2008. 05 to 2009. 01. We evaluate the results from phantom by substituting factors. We used one-day protocol and injected $^{99m}Tc$-ECD 925 MBq at both basal image acquisition and diamox image acquisition. Results: (1) The evaluation of phantom: After measuring counts from each detector, at basal image 41~46 kcount, stress image 79~90 kcount, subtraction image 40~47 kcount were detected. LEAP was about 102~113 kcount at basal image, 188~210 kcount at stress image and 94~103 at subtraction image kcount were detected. The SNR of LEHR subtraction image was decreased than LEHR basal image about 37%, the SNR of LEAP subtraction image was decreased than LEAP basal image about 17%. The ratio of gray matter versus white matter is 2.2:1 at LEHR basal image and 1.9:1 at subtraction, and at LEAP basal image was 2.4:1 and subtraction image was 2:1. (2) The evaluation of patient's image: the counts acquired by LEHR collimators are about 40~60 kcounts at basal image, and 80~100 kcount at stress image. It was proper to set FWHM as 7 mm at basal and stress image and 11mm at subtraction image. LEAP was about 80~100 kcount at basal image and 180~200 kcount at stress image. LEAP images could reduce blurring by setting FWHM as 5 mm at basal and stress images and 7 mm at subtraction image. At basal and stress image, LEHR image was superior than LEAP image. But in case of subtraction image like a phantom experiment, it showed rough image because SNR of LEHR image was decreased. On the other hand, in case of subtraction LEAP image was better than LEHR image in SNR and sensitivity. In all LEHR and LEAP collimator images, proper subset and iteration frequency was 8 times. Conclusions: We could archive more clear and high SNR subtraction image by using proper filter with LEAP collimator. In case of applying one day protocol and reconstructing by Flash 3D, we could consider application of LEAP collimator to acquire better subtraction image.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.32-41
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• 2004

Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.299-311
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• 1995

Platelets resemble monoaminergic neurons in several respects, i.e. the uptake of 5-HT and its inhibition, the subcellular storage and release of 5-HT, and the metabolism of aromatic amines brought about by monoamine oxidase. And the 5-HT content of rabbit platelets is well known to be about 40 times higher than that of human platelets. Therefore, this study was carried out to investigate the influences of amitriptyline (AMT) and sertraline (SRT) on the aggregation, contents of signaling second messengers, and protein phosphorylations of rabbit platelets in response to thrombin, 0.25 unit/ml, comparing with those of chlorpromazine (CPZ). Thrombin-induced aggregation was inhibited by SRT $(IC50:4.37{\times}10^{-5}\;M)$, CPZ $(IC50:5.76{\times}10^{-5}\;M)$, and AMT $(IC50:1.15{\times}10^{-4}\;M)$, respectively, and the aggregation by A23187 $(1.0\;{\mu}M)$ or PMA (320 nM) was also inhibited by SRT, CPZ, and AMT. AMT, SRT, and CPZ had little affects on basal contents of platelet $TXB_2$ and $PGE_2$, but all of them inhibited the thrombin-induced increase of $TXB_2$. Thrombin did not change the platelet contents of cAMP and cGMP. CPZ, AMT, and SRT produced the slight decrease of basal cAMP content, and their effects were not affected by thrombin-treatment. But SRT and AMT moderately increased the basal cGMP content, and the cGMP content of thrombin-stimulated platelets was gradually increased by the pretreatment with SRT, AMT, and CPZ. Particularly, the SRT-dependent increase of the cGMP content was notable. Platelet $Ins(1,4,5)P_3$ content was rapidly increased up to a plateau within 10 sec after thrombin-stimulation, AMT, SRT, and CPZ increased the basal $Ins(1,4,5)P_3$ content, and the thrombin-dependent increase was enhanced by pretreatment with CPZ and AMT, but was blunted by SRT. Platelet $[Ca^{2+}]_i$, was rapidly increased up to a peak level within 20 sec after thrombin-stimulation. The increase of $[Ca^{2+}]_i$ was sisnificantly inhibited by AMT, SRT, and CPZ. Thrombin- or PMA-induced phosphorylations of platelet $41{\sim}43\;kDa$ and 20 kDa proteins were significantly inhibited by AMT, SRT, and CPZ. These results suggest that the antiplatelet activities of AMT and CPZ may be considerably attributed to the inhibition of protein kinase C activity, and the activity of SRT may be associated with the inhibitory effect on the thrombin-induced increase of $Ins(1,4,5)P_3$ and the increasing effect on the cGMP content of ptatelets. Therefore, it seems to be evident that AMT and SRT may produce their antidepressant activity, at least, partly through the inhibition of protein kinase C activity or the increase of resting $Ins(1,4,5)P_3$, content and in case of SRT, to a lesser extent, via the increase of cGMP in the brain.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.123-135
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• 2012

Purpose: It is essential to minimize the movement of tumor due to respiratory movement at the time of respiration controlled radiotherapy of non-small cell lung cancer patient. Accordingly, this Study aims to evaluate the usefulness of restricted respiratory period by comparing and analyzing the treatment plans that apply free and restricted respiration period respectively. Materials and Methods: After having conducted training on 9 non-small cell lung cancer patients (tumor n=10) from April to December 2011 by using 'signal monitored-breathing (guided- breathing)' method for the 'free respiratory period' measured on the basis of the regular respiratory period of the patents and 'restricted respiratory period' that was intentionally reduced, total of 10 CT images for each of the respiration phases were acquired by carrying out 4D CT for treatment planning purpose by using RPM and 4-dimensional computed tomography simulator. Visual gross tumor volume (GTV) and internal target volume (ITV) that each of the observer 1 and observer 2 has set were measured and compared on the CT image of each respiratory interval. Moreover, the amplitude of movement of tumor was measured by measuring the center of mass (COM) at the phase of 0% which is the end-inspiration (EI) and at the phase of 50% which is the end-exhalation (EE). In addition, both observers established treatment plan that applied the 2 respiratory periods, and mean dose to normal lung (MDTNL) was compared and analyzed through dose-volume histogram (DVH). Moreover, normal tissue complication probability (NTCP) of the normal lung volume was compared by using dose-volume histogram analysis program (DVH analyzer v.1) and statistical analysis was performed in order to carry out quantitative evaluation of the measured data. Results: As the result of the analysis of the treatment plan that applied the 'restricted respiratory period' of the observer 1 and observer 2, there was reduction rate of 38.75% in the 3-dimensional direction movement of the tumor in comparison to the 'free respiratory period' in the case of the observer 1, while there reduction rate was 41.10% in the case of the observer 2. The results of measurement and comparison of the volumes, GTV and ITV, there was reduction rate of $14.96{\pm}9.44%$ for observer 1 and $19.86{\pm}10.62%$ for observer 2 in the case of GTV, while there was reduction rate of $8.91{\pm}5.91%$ for observer 1 and $15.52{\pm}9.01%$ for observer 2 in the case of ITV. The results of analysis and comparison of MDTNL and NTCP illustrated the reduction rate of MDTNL $3.98{\pm}5.62%$ for observer 1 and $7.62{\pm}10.29%$ for observer 2 in the case of MDTNL, while there was reduction rate of $21.70{\pm}28.27%$ for observer 1 and $37.83{\pm}49.93%$ for observer 2 in the case of NTCP. In addition, the results of analysis of correlation between the resultant values of the 2 observers, while there was significant difference between the observers for the 'free respiratory period', there was no significantly different reduction rates between the observers for 'restricted respiratory period. Conclusion: It was possible to verify the usefulness and appropriateness of 'restricted respiratory period' at the time of respiration controlled radiotherapy on non-small cell lung cancer patient as the treatment plan that applied 'restricted respiratory period' illustrated relative reduction in the evaluation factors in comparison to the 'free respiratory period.

• Sleep Medicine and Psychophysiology
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• v.22 no.2
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• pp.70-76
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• 2015

Background and Objectives: Insomnia is the most prevalent sleep disorder in the general population and is considered to be a disorder of hyperarousal. The aim of this study was to measure the psychophysiological responses in insomnia patients using a biofeedback system, and to compare them with results from normal healthy subjects. Materials and Methods: Eighty patients with primary insomnia (35 males and 45 females, average age $49.71{\pm}12.91years$) and 101 normal healthy controls (64 males and 37 females, average age $27.65{\pm}2.77$) participated in this study. Electromyography (EMG), heart rate (HR), skin conductance (SC), skin temperature (ST), and respiratory rate (RR) were recorded using a biofeedback system during 5 phases (baseline, stress 1, recovery 1, stress 2, recovery 2) of a stress reactivity test, and average values were calculated. Difference in values between the two groups in each corresponding phase was analyzed with independent t-test, and change in values across phases of the stress reactivity test was analyzed with paired t-test (all two-tailed, p<0.05). Results: Compared to normal controls, insomnia patients had higher EMG in all 5 phases (baseline : $7.72{\pm}3.88{\mu}V$ vs. $4.89{\pm}1.73{\mu}V$, t = -6.06, p<0.001 ; stress 1 : $10.29{\pm}5.16{\mu}V$ vs. $6.63{\pm}2.48{\mu}V$, t = -5.84, p<0.001 ; recovery 1 : $7.87{\pm}3.86{\mu}V$ vs. $5.17{\pm}2.17{\mu}V$, t = -5.61, p<0.001 ; stress 2 : $10.22{\pm}6.07{\mu}V$ vs. $6.98{\pm}2.98{\mu}V$, t = -4.37, p<0.001 ; recovery 2 : $7.88{\pm}4.25{\mu}V$ vs. $5.17{\pm}1.99{\mu}V$, t = -5.27, p<0.001). Change in heart rate across phases of the stress reactivity test were higher in normal controls than in insomnia patients (stress 1-baseline : $6.48{\pm}0.59$ vs. $3.77{\pm}0.59$, t = 3.22, p = 0.002 ; recovery 1- stress 1 : $-5.36{\pm}0.0.59$ vs. $-3.16{\pm}0.47$, t = 2.91, p = 0.004 ; stress 2-recovery 1 : $8.45{\pm}0.61$ vs. $4.03{\pm}0.47$, t = 5.72, p<0.001 ; recovery 2-stress 2 : $-8.56{\pm}0.65$ vs. $4.02{\pm}0.51$, t = -5.31, p<0.001). Conclusion: Psychophysiological profiles of insomnia patients in a stress reactivity test were different from those of normal healthy controls. These results suggest that the sympathetic nervous system is more highly activated in insomnia patients.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Progress in Medical Physics
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• v.22 no.3
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• pp.140-147
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• 2011

The purpose of this study was to estimate internal motion using molecular sieve for quantitative improvement of lung tumor and to localize lung tumor in the small animal PET image by evaluated data. Internal motion has been demonstrated in small animal lung region by molecular sieve contained radioactive substance. Molecular sieve for internal lung motion target was contained approximately 37 kBq Cu-64. The small animal PET images were obtained from Siemens Inveon scanner using external trigger system (BioVet). SD-Rat PET images were obtained at 60 min post injection of FDG 37 MBq/0.2 mL via tail vein for 20 min. Each line of response in the list-mode data was converted to sinogram gated frames (2~16 bin) by trigger signal obtained from BioVet. The sinogram data was reconstructed using OSEM 2D with 4 iterations. PET images were evaluated with count, SNR, FWHM from ROI drawn in the target region for quantitative tumor analysis. The size of molecular sieve motion target was $1.59{\times}2.50mm$. The reference motion target FWHM of vertical and horizontal was 2.91 mm and 1.43 mm, respectively. The vertical FWHM of static, 4 bin and 8 bin was 3.90 mm, 3.74 mm, and 3.16 mm, respectively. The horizontal FWHM of static, 4 bin and 8 bin was 2.21 mm, 2.06 mm, and 1.60 mm, respectively. Count of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.10, 4.83, 5.59, 5.38, and 5.31, respectively. The SNR of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.18, 4.05, 4.22, 3.89, and 3.58, respectively. The FWHM were improved in accordance with gate number increase. The count and SNR were not proportionately improve with gate number, but shown the highest value in specific bin number. We measured the optimal gate number what minimize the SNR loss and gain improved count when imaging lung tumor in small animal. The internal motion estimation provide localized tumor image and will be a useful method for organ motion prediction modeling without external motion monitoring system.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.83-89
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• 2010

Purpose: The Wide Beam Reconstruction (WBR) algorithms that UltraSPECT, Ltd. (U.S) has provides solutions which improved image resolution by eliminating the effect of the line spread function by collimator and suppression of the noise. It controls the resolution and noise level automatically and yields unsurpassed image quality. The aim of this study is WBR of whole body bone scan in usefulness of clinical application. Materials and Methods: The standard line source and single photon emission computed tomography (SPECT) reconstructed spatial resolution measurements were performed on an INFINA (GE, Milwaukee, WI) gamma camera, equipped with low energy high resolution (LEHR) collimators. The total counts of line source measurements with 200 kcps and 300 kcps. The SPECT phantoms analyzed spatial resolution by the changing matrix size. Also a clinical evaluation study was performed with forty three patients, referred for bone scans. First group altered scan speed with 20 and 30 cm/min and dosage of 740 MBq (20 mCi) of $^{99m}Tc$-HDP administered but second group altered dosage of $^{99m}Tc$-HDP with 740 and 1,110 MBq (20 mCi and 30 mCi) in same scan speed. The acquired data was reconstructed using the typical clinical protocol in use and the WBR protocol. The patient's information was removed and a blind reading was done on each reconstruction method. For each reading, a questionnaire was completed in which the reader was asked to evaluate, on a scale of 1-5 point. Results: The result of planar WBR data improved resolution more than 10%. The Full-Width at Half-Maximum (FWHM) of WBR data improved about 16% (Standard: 8.45, WBR: 7.09). SPECT WBR data improved resolution more than about 50% and evaluate FWHM of WBR data (Standard: 3.52, WBR: 1.65). A clinical evaluation study, there was no statistically significant difference between the two method, which includes improvement of the bone to soft tissue ratio and the image resolution (first group p=0.07, second group p=0.458). Conclusion: The WBR method allows to shorten the acquisition time of bone scans while simultaneously providing improved image quality and to reduce the dosage of radiopharmaceuticals reducing radiation dose. Therefore, the WBR method can be applied to a wide range of clinical applications to provide clinical values as well as image quality.