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    Representative transverse CT images of a clinically normal Holstein calf. The 3 images are from the same CT slice obtained at a level that included the mandibular condyle. The calf was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm. A—Conventional transverse CT image (window level, 40 Hounsfield units; window width, 80 Hounsfield units). B—Perfusion CT color map of CBF (mL/100 g/min) merged with the image in panel A. C—Perfusion CT color map of CBV (mL/100 g) merged with the image in panel A. The color scales placed on the left sides of panels B and C indicate the values of each variable. The CBF and CBV values of the cerebral cortex are higher than those of the white matter.

  • 1. Saegerman C, Claes L, Dewaele A, et al. Differential diagnosis of neurologically expressed disorders in Western European cattle. Rev Sci Tech 2003;22:83102.

    • Search Google Scholar
    • Export Citation
  • 2. Eastwood JD, Lev MH, Azhari T, et al. CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke. Radiology 2002;222:227236.

    • Search Google Scholar
    • Export Citation
  • 3. Sasaki M, Kudo K, Honjo K, et al. Prediction of infarct volume and neurologic outcome by using automated multiparametric perfusion-weighted magnetic resonance imaging in a primate model of permanent middle cerebral artery occlusion. J Cereb Blood Flow Metab 2011;31:448456.

    • Search Google Scholar
    • Export Citation
  • 4. Fan GG, Deng QL, Wu ZH, et al. Usefulness of diffusion/perfusion-weighted MRI in patients with non-enhancing supratentorial brain gliomas: a valuable tool to predict tumour grading? Br J Radiol 2006;79:652658.

    • Search Google Scholar
    • Export Citation
  • 5. Marco de Lucas E, González Mandly A, Gutiérrez A, et al. Computed tomography perfusion usefulness in early imaging diagnosis of herpes simplex virus encephalitis. Acta Radiol 2006;47:878881.

    • Search Google Scholar
    • Export Citation
  • 6. König M. Brain perfusion CT in acute stroke: current status. Eur J Radiol 2003;45:S11S22.

  • 7. Kishimoto M, Tsuji Y, Katabami N, et al. Measurement of canine pancreatic perfusion using dynamic computed tomography: influence of input-output vessels on deconvolution and maximum slope methods. Eur J Radiol 2011;77:175181.

    • Search Google Scholar
    • Export Citation
  • 8. Tsuji Y, Yamamoto H, Yazumi S, et al. Perfusion computerized tomography can predict pancreatic necrosis in early stages of severe acute pancreatitis. Clin Gastroenterol Hepatol 2007;5:14841492.

    • Search Google Scholar
    • Export Citation
  • 9. Nambu K, Takehara R, Terada T. A method of regional cerebral blood perfusion measurement using dynamic CT with an iodinated contrast medium. Acta Neurol Scand Suppl 1996;166:2831.

    • Search Google Scholar
    • Export Citation
  • 10. Konold T, Sivam SK, Ryan J, et al. Analysis of clinical signs associated with bovine spongiform encephalopathy in casualty slaughter cattle. Vet J 2006;171:438444.

    • Search Google Scholar
    • Export Citation
  • 11. Cockcroft PD. The similarity of the physical sign frequencies of bovine spongiform encephalopathy and selected differential diagnoses. Vet J 2004;167:175180.

    • Search Google Scholar
    • Export Citation
  • 12. Wintermark M, Maeder P, Thiran JP, et al. Quantitative assessment of regional cerebral blood flows by perfusion CT studies at low injection rates: a critical review of the underlying theoretical models. Eur Radiol 2001;11:12201230.

    • Search Google Scholar
    • Export Citation
  • 13. Huisman TA, Sorensen AG. Perfusion-weighted magnetic resonance imaging of the brain: techniques and application in children. Eur Radiol 2004;14:5972.

    • Search Google Scholar
    • Export Citation
  • 14. Takahashi T, Shirane R, Sato S, et al. Developmental changes of cerebral blood flow and oxygen metabolism in children. AJNR Am J Neuroradiol 1999;20:917922.

    • Search Google Scholar
    • Export Citation
  • 15. Rubinstein M, Denays R, Ham HR, et al. Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT. J Nucl Med 1989;30:19821985.

    • Search Google Scholar
    • Export Citation
  • 16. Omata N, Murata T, Maruoka N, et al. Different mechanisms of hypoxic injury on white matter and gray matter as revealed by dynamic changes in glucose metabolism in rats. Neurosci Lett 2003;353:148152.

    • Search Google Scholar
    • Export Citation
  • 17. Kan R, Takahashi Y, Sato K, et al. Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease. Jpn J Psychiatry Neurol 1992;46:175179.

    • Search Google Scholar
    • Export Citation
  • 18. Tsuka T, Taura Y, Okamura S, et al. Imaging diagnosis– polioencephalomalacia in a calf. Vet Radiol Ultrasound 2008;49:149151.

  • 19. Suzuki M, Sitizyo K, Takeuchi T, et al. Electroencephalogram of Japanese Black calves affected with cerebrocortical necrosis. Nippon Juigaku Zasshi 1990;52:10771087.

    • Search Google Scholar
    • Export Citation
  • 20. Kitabayashi Y, Ueda H, Narumoto J, et al. Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study. Psychiatry Clin Neurosci 2002;56:6570.

    • Search Google Scholar
    • Export Citation

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Perfusion computed tomographic measurements of cerebral blood flow variables in live Holstein calves

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  • 1 Laboratory of Veterinary Diagnostic Imaging, Cooperative Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwai-cho, 3-5-8, Fuchu, Tokyo 183-8509, Japan.
  • | 2 Laboratory of Clinical Pathology, Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Kohrimoto, Kagoshima 890-0065, Japan.
  • | 3 Laboratory of Veterinary Radiology, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan.

Abstract

OBJECTIVE To measure cerebral blood flow (CBF) and cerebral blood volume (CBV) by means of perfusion CT in clinically normal Holstein calves.

ANIMALS 9 Holstein calves.

PROCEDURES Each of the 9 calves (mean age, 20.2 days) was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm.

RESULTS Among the 9 calves, the mean ± SD CBF in the cerebral cortex, white matter, and thalamus was 44.3 ± 10.3 mL/100 g/min, 36.1 ± 7.5 mL/100 g/min, and 40.3 ± 7.5 mL/100 g/min, respectively. The CBF in white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex, white matter, and thalamus was 6.8 ± 1.0 mL/100 g, 5.2 ± 1.0 mL/100 g, and 5.7 ± 0.7 mL/100 g, respectively. The CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus.

CONCLUSIONS AND CLINICAL RELEVANCE Measurement of CBF and CBV in clinically normal calves by means of perfusion CT was feasible. The data obtained may be useful as baseline values for use in future research or for comparison with findings from calves with CNS diseases. Investigations to determine the lower limit of blood flow at which brain function can still be restored are warranted.

Abstract

OBJECTIVE To measure cerebral blood flow (CBF) and cerebral blood volume (CBV) by means of perfusion CT in clinically normal Holstein calves.

ANIMALS 9 Holstein calves.

PROCEDURES Each of the 9 calves (mean age, 20.2 days) was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm.

RESULTS Among the 9 calves, the mean ± SD CBF in the cerebral cortex, white matter, and thalamus was 44.3 ± 10.3 mL/100 g/min, 36.1 ± 7.5 mL/100 g/min, and 40.3 ± 7.5 mL/100 g/min, respectively. The CBF in white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex, white matter, and thalamus was 6.8 ± 1.0 mL/100 g, 5.2 ± 1.0 mL/100 g, and 5.7 ± 0.7 mL/100 g, respectively. The CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus.

CONCLUSIONS AND CLINICAL RELEVANCE Measurement of CBF and CBV in clinically normal calves by means of perfusion CT was feasible. The data obtained may be useful as baseline values for use in future research or for comparison with findings from calves with CNS diseases. Investigations to determine the lower limit of blood flow at which brain function can still be restored are warranted.

The prevalence of and variations in intracranial disease in cattle are largely unknown, unlike the available information regarding humans, dogs, and cats with intracranial disease.1 In addition, there are few noninvasive (antemortem) imaging tests for bovids with brain disorders, and the use of diagnostic imaging for early disease detection and diagnosis determination is not well documented. As a result, cerebral functional imaging methods have not been introduced into bovine clinical practice.

For humans, functional imaging methods involving CT2 or MRI3 have enabled the quantification of CBF. Thus, it is now possible to obtain a diagnosis, assess outcome after treatment, and provide prognostic predictions for intracranial disorders such as acute stroke,2 brain tumors,4 and encephalitis5 in humans. If such functional imaging methods were available for use in cattle, antemortem diagnosis, early disease detection, assessment of treatment effects, and the detection of unsuspected disease for specific brain disorders such as encephalitis and bovine spongiform encephalopathy could be achieved. The CBF data from the functional imaging could be used to complement serologic findings and allow the collation of epidemiological data.

Therefore, our interest was focused on the potential of perfusion CT as a functional diagnostic imaging method for evaluation of bovine cerebral disease. Perfusion CT is a contrast CT examination that enables rapid quantitative estimation of CBF and CBV6 after injection of a small volume of contrast medium.7,8 Further, it is cost effective and relatively easy to perform in cattle. The purpose of the study reported here was to measure CBF and CBV in clinically normal calves as a first step toward the study of cerebral functional imaging by means of perfusion CT in cattle.

Materials and Methods

Animals

Nine clinically normal Holstein calves were used in the study. The calves' mean age was 20.2 days (range, 16 to 24 days) and mean body weight was 36.1 kg (range, 33 to 40 kg). There were 6 males and 3 females in the group. Each calf underwent perfusion CT evaluation of CBF and CBV once. Prior to the experiments, neurologic examinations and blood tests (a CBC and assessments of BUN concentration; serum concentrations of creatinine, glucose, and NH3; and serum activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and creatine kinase) were performed. Experiments were performed after each calf was anesthetized by IV injection of pentobarbital sodium (14 mg/kg) and intubated. Each calf breathed simultaneously; inhalational anesthesia was not necessary to achieve the CT evaluations. Oxygen saturation (measured by pulse oximetry), end-tidal carbon dioxide concentration, rectal temperature, and heart rate were monitored during anesthesia. For each calf, a 16-gauge catheter was placed in the right jugular vein as an injection route for the contrast medium. The catheter was removed after recovery from anesthesia. No complications developed during or after the experiments, and all calves recovered from anesthesia uneventfully. The experiments were approved by the animal experiments committee of the Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.

Perfusion CT procedure and image analysis

The CT images were acquired with a multi– detector row CT.a Each anesthetized calf was placed in sternal recumbency, and the head was positioned with the cerebral base parallel to the CT table. Sodium iothalamateb (300 mg/kg) was injected via the jugular catheter at a rate of 4.0 mL/s by use of a dual-head auto-injector.c Dynamic CT scanning at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for a period of 100 seconds. The perfusion CT scanning settings were as follows: 80 kV, 150 mA, 1.0 s/rotation, 4.0-second interval, and slice thickness of 5.0 mm. The data were analyzed with a deconvolution method7,9 and a commercially available software packaged for blood flow analysis. The anterior cerebral artery and lateral sinus were selected as the input artery and the output vein, respectively.

The CBF (mL/100 g/min) and CBV (mL/100 g) were measured in transverse CT sections of the cerebral cortex, the white matter of the parietal lobe and temporal lobe, and the thalamus. Five circular ROIs were drawn on each side of the cerebral cortex, the white matter of the parietal lobe and temporal lobe, and the thalamus. The area of each ROI was 15.0 mm2. For each variable in each calf, measurements were performed 3 times, and the mean value was calculated. Overall results for all calves are reported as means and SDs. After the perfusion CT examination, a routine contrast CT examination was performed with injection of 600 mg of sodium iothalamate/kg to confirm the absence of fundamental abnormalities or anomalies in the brain. The routine contrast CT scanning settings were as follows: 120 kV, 150 mA, 0.5 s/rotation, slice thickness of 0.5 mm, and use of the abdominal and bone reconstruction function.

Statistical analysis

Differences in CBF and CBV among the cerebral cortex, white matter, and thalamus were analyzed with a post-hoc Bonferroni-Dunn test. Differences in CBF and CBV between the right and left sides of the brain were analyzed with the Mann–Whitney U test. Correlation coefficients for CBF or CBV and age and body weight were calculated by the Spearman rank method. A value of P < 0.05 was considered significant. Statistical analyses were performed with computer software.e

Results

The experiments with all 9 calves were successfully completed, and CT color maps of their heads were obtained (Figure 1). For CBF and CBV, mean values were calculated and their minimum values recorded (Table 1). There were no significant differences in CBF or CBV between the right and left sides of the brain; therefore, the mean values of the CBF and CBV for each calf were calculated from 10 ROIs (ie, from 5 ROIs of the right side and 5 ROIs of the left side of the brain). Overall mean values for the group of 9 calves were then calculated. The mean CBF in the white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus. In addition, there were no significant correlations between CBF or CBV and age or body weight. No abnormalities were detected during the routine contrast CT examination of the brain.

Figure 1—
Figure 1—

Representative transverse CT images of a clinically normal Holstein calf. The 3 images are from the same CT slice obtained at a level that included the mandibular condyle. The calf was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm. A—Conventional transverse CT image (window level, 40 Hounsfield units; window width, 80 Hounsfield units). B—Perfusion CT color map of CBF (mL/100 g/min) merged with the image in panel A. C—Perfusion CT color map of CBV (mL/100 g) merged with the image in panel A. The color scales placed on the left sides of panels B and C indicate the values of each variable. The CBF and CBV values of the cerebral cortex are higher than those of the white matter.

Citation: American Journal of Veterinary Research 79, 2; 10.2460/ajvr.79.2.177

Table 1—

Values of CBF and CBV determined by means of perfusion CT in 9 clinically normal Holstein calves.

 CBF (mL/100 g/min)CBV (mL/100 g)
Brain regionMean ± SDMinimum valueMean ± SDMinimum value
Cerebral cortex44.3 ± 10.331.96.8 ± 1.0*5.2
White matter36.1 ± 7.5*28.35.2 ± 1.03.6
Thalamus40.3 ± 7.530.65.7 ± 0.74.9

Each calf was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was employed as an analytic algorithm. The CBF (mL/100 g/min) and CBV (mL/100 g) were measured in transverse CT sections of the cerebral cortex, the white matter of the parietal lobe and temporal lobe, and the thalamus. Five 15.0-mm2 ROIs were drawn on each side of the cerebral cortex, the white matter of the parietal lobe and temporal lobe, and the thalamus. Measurements were performed 3 times, and the mean value was calculated. There were no significant differences in CBF or CBV between the right and left sides of the brain; therefore, the mean values of the CBF and CBV for each calf were calculated from 10 ROIs (ie, from 5 ROIs of the right side and 5 ROIs of the left side of the brain). Overall mean values for the group of 9 calves were then calculated.

Within a column, value is significantly different from that for other brain regions.

Discussion

Currently, there are far fewer diagnostic tools for antemortem assessment of neurologic disorders in cattle10 than there are for such assessments in humans and companion animals. Moreover, there are no tools for monitoring macroscopic changes in bovine brain tissue over time. Additionally, numerous normal and abnormal brain vessel structures in cattle have not been defined in veterinary textbooks.11 Therefore, for the purpose of food safety, collection of imaging data to correlate with pathological and serologic findings would be useful for evaluation of pathological changes in the brains of animals that are included in the food chain.

In the present study, CBF and CBV values for 9 clinically normal Holstein calves were determined by means of perfusion CT. Results indicated that the mean CBF in the white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus. Similar differences in these variables between the cerebral cortex and white matter have been identified in humans.12 Although perfusion CT requires administration of a contrast medium, this method is still applicable to cattle because of the short examination time.

In the present study, the CBF values of bovine gray matter were similar to those in humans.12 However, the CBF value of white matter was higher in cattle than in humans.12 Therefore, the ratio of gray matter CBF to white matter CBF was lower in cattle than that reported for humans.12 Further, the ratio of gray matter CBV to white matter CBV was lower than previously reported for humans.12 There are 2 possible reasons for these differences—age and species differences. Blood flow to white matter is reportedly higher during the brain's maturation process than at completion of maturation.13 In addition, CBF is lower in neonates than in children and adults. Compared with findings for neonates, there is a notable increase in CBF in infants, with a peak at the age of 7 years.14 Furthermore, the distribution pattern of CBF differs with age.15 Given these facts, the gray matter CBF- or CBV-to-white matter CBF or CBV ratios may have been low in the selected CT slices examined in the present study because the calves were young (mean age, 20.2 days). Future studies should focus on generating reference ranges for age- and region-specific blood flow variables in cattle.

With regard to the influence of the differences in blood flow variables among animal species, the white matter volume itself differs between humans and other animals.16 Therefore, there may be fundamental differences in CBF and CBV in white matter of humans and cattle.

In human medicine, CBF and CBV are used to develop differential diagnosis lists, monitor treatment outcomes, and provide a prognosis for cases of acute stroke,2 brain tumor,4 encephalitis,5 and Creutzfeldt-Jakob disease.17 Potential applications of perfusion CT in cattle include evaluation of animals with CCN or encephalitis. In cases of CCN, the ischemia (low CBF) caused by lactic acidosis is thought to be involved in the laminar necrosis of the cerebral cortex.18 In addition, it is important to diagnose CCN during the early stage of the disease because parenteral treatment with thiamine when early clinical signs are present appears to have curative potential.19 With respect to encephalitis in humans, temporal increases in CBF are caused by inflammation, and CBF has been shown to decrease to within the normal range after treatment. Therefore, perfusion CT may be applicable to formulation of differential diagnoses, monitoring of treatment outcomes, and stage classification in cattle with brain disorders.6,20

Two limitations of the present study were related to the IV administration of an iodinated ionic contrast medium and pentobarbital sodium. Although both agents are not considered state of the art, they were chosen for economic reasons. The present study was an initial exploration of the feasibility of cerebral functional imaging in cattle, which are economically important animals; therefore, cost was considered in development of the experimental protocol. For example, the ionic contrast medium and pentobarbital sodium that were used were less expensive than the agents that we would normally use. However, in future assessments, nonionic contrast medium should be administered because it is safer to use in animals. In addition, the effect of pentobarbital on circulatory dynamics is not negligible. Therefore, future research should focus on establishing perfusion CT methods that involve anesthetics that have a minimal effect on circulatory dynamics, with strict monitoring of the cardiopulmonary status of cattle.

To our knowledge, this is the first study to determine perfusion CT-derived values for CBF and CBV in clinically normal calves. These data may be useful as baseline values for use in future research or for comparison with findings from calves with CNS diseases. Moreover, with further refinement of the technique, perfusion CT may ultimately represent a diagnostic and prognostic tool for use in cattle with brain disorders, particularly if the lower limit of blood flow at which point brain function can still be restored is determined.

Acknowledgments

The authors declare there were no conflicts of interest and no outside financial support.

ABBREVIATIONS

CBF

Cerebral blood flow

CBV

Cerebral blood volume

CCN

Cerebrocortical necrosis

Footnotes

a.

Asteion Super 4, Toshiba, Tochigi, Japan.

b.

Conray 400, Daiichi Sankyo Co Ltd, Tokyo, Japan.

c.

Dual Shot GX, Nemoto Kyorindo, Tokyo, Japan.

d.

CBP study, Toshiba, Tochigi, Japan.

e.

SPSS, version 22, SPSS Inc, Chicago, Ill.

References

  • 1. Saegerman C, Claes L, Dewaele A, et al. Differential diagnosis of neurologically expressed disorders in Western European cattle. Rev Sci Tech 2003;22:83102.

    • Search Google Scholar
    • Export Citation
  • 2. Eastwood JD, Lev MH, Azhari T, et al. CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke. Radiology 2002;222:227236.

    • Search Google Scholar
    • Export Citation
  • 3. Sasaki M, Kudo K, Honjo K, et al. Prediction of infarct volume and neurologic outcome by using automated multiparametric perfusion-weighted magnetic resonance imaging in a primate model of permanent middle cerebral artery occlusion. J Cereb Blood Flow Metab 2011;31:448456.

    • Search Google Scholar
    • Export Citation
  • 4. Fan GG, Deng QL, Wu ZH, et al. Usefulness of diffusion/perfusion-weighted MRI in patients with non-enhancing supratentorial brain gliomas: a valuable tool to predict tumour grading? Br J Radiol 2006;79:652658.

    • Search Google Scholar
    • Export Citation
  • 5. Marco de Lucas E, González Mandly A, Gutiérrez A, et al. Computed tomography perfusion usefulness in early imaging diagnosis of herpes simplex virus encephalitis. Acta Radiol 2006;47:878881.

    • Search Google Scholar
    • Export Citation
  • 6. König M. Brain perfusion CT in acute stroke: current status. Eur J Radiol 2003;45:S11S22.

  • 7. Kishimoto M, Tsuji Y, Katabami N, et al. Measurement of canine pancreatic perfusion using dynamic computed tomography: influence of input-output vessels on deconvolution and maximum slope methods. Eur J Radiol 2011;77:175181.

    • Search Google Scholar
    • Export Citation
  • 8. Tsuji Y, Yamamoto H, Yazumi S, et al. Perfusion computerized tomography can predict pancreatic necrosis in early stages of severe acute pancreatitis. Clin Gastroenterol Hepatol 2007;5:14841492.

    • Search Google Scholar
    • Export Citation
  • 9. Nambu K, Takehara R, Terada T. A method of regional cerebral blood perfusion measurement using dynamic CT with an iodinated contrast medium. Acta Neurol Scand Suppl 1996;166:2831.

    • Search Google Scholar
    • Export Citation
  • 10. Konold T, Sivam SK, Ryan J, et al. Analysis of clinical signs associated with bovine spongiform encephalopathy in casualty slaughter cattle. Vet J 2006;171:438444.

    • Search Google Scholar
    • Export Citation
  • 11. Cockcroft PD. The similarity of the physical sign frequencies of bovine spongiform encephalopathy and selected differential diagnoses. Vet J 2004;167:175180.

    • Search Google Scholar
    • Export Citation
  • 12. Wintermark M, Maeder P, Thiran JP, et al. Quantitative assessment of regional cerebral blood flows by perfusion CT studies at low injection rates: a critical review of the underlying theoretical models. Eur Radiol 2001;11:12201230.

    • Search Google Scholar
    • Export Citation
  • 13. Huisman TA, Sorensen AG. Perfusion-weighted magnetic resonance imaging of the brain: techniques and application in children. Eur Radiol 2004;14:5972.

    • Search Google Scholar
    • Export Citation
  • 14. Takahashi T, Shirane R, Sato S, et al. Developmental changes of cerebral blood flow and oxygen metabolism in children. AJNR Am J Neuroradiol 1999;20:917922.

    • Search Google Scholar
    • Export Citation
  • 15. Rubinstein M, Denays R, Ham HR, et al. Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT. J Nucl Med 1989;30:19821985.

    • Search Google Scholar
    • Export Citation
  • 16. Omata N, Murata T, Maruoka N, et al. Different mechanisms of hypoxic injury on white matter and gray matter as revealed by dynamic changes in glucose metabolism in rats. Neurosci Lett 2003;353:148152.

    • Search Google Scholar
    • Export Citation
  • 17. Kan R, Takahashi Y, Sato K, et al. Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease. Jpn J Psychiatry Neurol 1992;46:175179.

    • Search Google Scholar
    • Export Citation
  • 18. Tsuka T, Taura Y, Okamura S, et al. Imaging diagnosis– polioencephalomalacia in a calf. Vet Radiol Ultrasound 2008;49:149151.

  • 19. Suzuki M, Sitizyo K, Takeuchi T, et al. Electroencephalogram of Japanese Black calves affected with cerebrocortical necrosis. Nippon Juigaku Zasshi 1990;52:10771087.

    • Search Google Scholar
    • Export Citation
  • 20. Kitabayashi Y, Ueda H, Narumoto J, et al. Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study. Psychiatry Clin Neurosci 2002;56:6570.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Address correspondence to Dr. Kishimoto (285copernicium@gmail.com).