Magn Reson Med Sci, Vol. 14, No. 1, pp. 51–56, 2015
doi:10.2463/mrms.2013-0126
© 2014 Japanese Society for Magnetic Resonance in Medicine
MAJOR PAPER
Cerebral Relaxation Times from Postmortem MR Imaging of Adults Kazuya TASHIRO1*, Seiji SHIOTANI2, Tomoya KOBAYASHI1, Kazunori KAGA1, Hajime SAITO1, Satoka SOMEYA1, Katsumi MIYAMOTO1, and Hideyuki HAYAKAWA3 1
Department of Radiological Technology, Tsukuba Medical Center Hospital 1–3–1 Amakubo, Tsukuba, Ibaraki 305–8558, Japan 2 Department of Radiology, Tsukuba Medical Center Hospital 3 Department of Forensic Medicine, Tsukuba Medical Examiner’s Office (Received December 13, 2013; Accepted July 16, 2014; published online December 15, 2014)
Purpose: We measured T 1 and T 2 values of cerebral postmortem magnetic resonance (PMMR) imaging and compared the data of cadavers with that of living human subjects. Materials and Methods: We performed PMMR imaging of the brains of 30 adults (22 men, 8 women; mean age, 58.2 years) whose deaths were for reasons other than brain injury or disease at a mean of 29.4 hours after death. Before imaging, the bodies were kept in cold storage at 4°C (mean rectal temperature, 15.6°C). We measured T 1 and T 2 values in the brain bilaterally at 5 sites (bilateral caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe) and compared the data of PMMR imaging with that from MR imaging of the corresponding sites in 24 healthy volunteers (9 men, 15 women; mean age, 51.8 years). We also investigated the influence of body temperature on T 1 and T 2 values. Results: Compared with MR imaging findings in the living subjects, PMMR imaging showed significantly shorter T 1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe and significantly longer T 2 values in the gray matter and white matter of the frontal lobe; T 2 values in the caudate nucleus, putamen, and thalamus showed no such differences. T 1 values correlated significantly with body temperature in all 5 brain sites measured, but T 2 values did not. Conclusion: Compared with findings of cerebral MR imaging in living adult subjects, those of PMMR imaging tended to demonstrate shorter T 1 values and longer T 2 values. We attribute this to increased water content of tissue, reduced pH, and reduced body temperature after death. Keywords: brain, in vivo, low body temperature, postmortem cross-sectional imaging, postmortem magnetic resonance imaging (PMMR imaging) imaging findings require analyses of quantified data. Several papers have described PMMR imaging findings in the brain, 8,11–14 and PMMR imaging and ADC values of the adult brain,12,13 T 1 and T 2 values of the pediatric brain, 14 and T 1 and T 2 values of the rat and human adult brain in vitro have been reported. 15,16 However, we believe there are no published data regarding quantitative T 1 and T 2 values in vivo of cerebral PMMR imaging of adults. Herein, we report the T 1 and T 2 values of cerebral MR imaging of deceased adults and compare them with those of living adult subjects.
Introduction The worldwide decline in the rate of conventional autopsies has led to the need for and frequency of postmortem imaging as a complementary, supplementary, or alternative method for autopsy.1–7 Postmortem magnetic resonance (PMMR) imaging has shown that MR signals and image contrast change after death. 8 –10 Optimization of parameters for PMMR imaging and accurate interpretation of *Corresponding author, Phone: +81-29-851-3511, Fax: +8129-858-2773, E-mail: [email protected] 51
52
Materials and Methods Subjects We examined PMMR imaging data of 30 adults (22 men, 8 women; aged 26 to 96 years, mean 58.2 years) who died suddenly and unexpectedly and had no abnormal results of neuropathological examination of the brain. Their bodies were kept in cold storage at 4°C and subjected to PMMR imaging 12 to 96 hours after confirmation of death (mean 29.4 hours). Their rectal temperatures, measured immediately after PMMR imaging with an industrial thermometer (7-257-01, AS ONE, Osaka, Japan) were 5 to 30°C (mean 15.6°C). Autopsy was performed on each subject after PMMR imaging. Causes of death were 5 cases each of ischemic heart disease, suffocation, and acute heart failure, 3 cases of drowning in the bathtub; 2 cases each of malnutrition, acute drug intoxication, cervical spine injury, and acute alcohol intoxication, and one case each of hemorrhagic gastric ulcer, diabetic ketoacidosis, traumatic rupture of the aorta, and ileus. For comparison, we also examined MR imaging data of 24 healthy volunteers (9 men, 15 women; aged 43 to 79 years, mean 51.8 years) who gave written informed consent to participate in our study. None of these subjects had intracranial morphological abnormalities on MR imaging, neurological disease, history of severe head trauma, or psychiatric disorder. Mean age did not differ significantly between the deceased and living subjects. Scan conditions With the permission of our institutional ethics committee, we performed PMMR imaging and MR imaging of volunteers using the same 1.5-tesla MR imaging clinical scanner (Avanto, Siemens, Erlangen, Germany) with a dedicated 12-element phased-array head coil. We measured T 1 and T 2 values with a relaxation time (RT) map creation tool (syngo MapIt, Siemens, Erlangen, Germany). 17 Table 1 shows the scan parameters for the brain. Analyses A radiological technologist (K.T.) with 5 years of experience defined circular regions of interest (ROIs) of 5 mm 2 in the brain bilaterally in the caudate nucleus, putamen, thalamus and gray matter and white matter in the frontal lobes at the level of the basal ganglia (Fig. 1). Statistical analyses were performed using statistical software (Excel 2010, Microsoft, Redmond, WA, USA) with Statcel 2 (OMS, Tokyo, Japan) add-in software. Parametric statistics (arithmetic
K. Tashiro et al.
Table 1. Scan parameters of postmortem magnetic resonance (PMMR) imaging based on the syngo MapIt method (Siemens Medical Systems, Erlangen, Germany) Scan parameters
T1 map
T2 map
TR/TE (ms)
15/1.86
2000/30, 60, 90, 120, 150 180° 4/0.8 0.86 © 0.86 220 4.6 11
Flip angle Slice thickness/gap (mm) Matrix size (mm) Field of view (FOV) (mm) Scanning time (min) Number of slices
5°, 26° 3/0 0.86 © 0.86 220 2.7 22 (3D)
TE, echo time; TR, repetition time; 3D, 3-dimensional
Fig. 1. Regions of interest (ROIs) placed at the level of the basal ganglia on postmortem magnetic resonance (MR) images. ROIs were placed bilaterally on the 1) caudate nucleus, 2) putamen, 3) thalamus, 4) frontal gray matter, and 5) frontal white matter.
mean value « standard deviation [SD]) and Student’s t test were used with a significance value of p < 0.05 for group differences. We compared measured RT values between the deceased and living subjects and investigated the extent of the influence of differences in rectal temperature on T 1 and T 2 values. The relationships among T 1 values, T2 values, and rectal temperatures were statistically analyzed with Pearson’s correlation coefficient using the least squares method.
Magnetic Resonance in Medical Sciences
Cerebral MR Relaxation Time of the Dead
Results We observed no specific abnormality, except for signal intensity and contrast, between cerebral PMMR imaging and MR imaging of living subjects. T 1 and T 2 values did not differ significantly between the bilateral hemispheres (p Ú 0.05), so we averaged values from both hemispheres. Table 2 shows mean T 1 and T 2 values for the adult brain. Compared with the cerebral MR imaging of the living subjects, PMMR imaging showed significantly shorter T 1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe. T 2 values were significantly longer in the gray matter and white matter of the frontal lobe, but no such significant differences were found in the caudate nucleus, putamen, and thalamus. With PMMR imaging, T 1 values correlated significantly with rectal temperature for the 5 sites of the brain measured (Fig. 2a–e), but T 2 values did not (Fig. 3a–e).
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Table 2. Differences in relaxation time on magnetic resonance (MR) imaging between postmortem and living bodies
Caudate nucleus Putamen Thalamus Frontal gray matter Frontal white matter
T1 [ms]
T2 [ms]
Postmortem (Living body)
Postmortem (Living body)
955 « 104 (1250 « 81)* 855 « 100 (1126 « 54)* 740 « 74 (1230 « 74)* 935 « 88 (1209 « 94)* 623 « 56 (707 « 40)*
84.1 « 6.2 (86.5 « 2.4) 74.5 « 7.3 (73.7 « 3.2) 82.7 « 6.1 (82.0 « 3.3) 116.8 « 11.2 (95.4 « 6.1)* 96.1 « 5.9 (78.1 « 3.0)*
*indicates statistically significant difference between postmortem and living bodies
Fig. 2. Relationship between T 1 values and rectal temperatures of deceased subjects in the a) caudate nucleus, b) putamen, c) thalamus, d) frontal gray matter, and e) frontal white matter. Vol. 14 No. 1, 2015
54
K. Tashiro et al.
Fig. 3. Relationship between T2 values and rectal temperature of deceased subjects in the a) caudate nucleus, b) putamen, c) thalamus, d) frontal gray matter, and e) frontal white matter.
Discussion Compared with the findings of cerebral MR imaging of living subjects, T 1 values tended to be shorter and T 2 values prolonged on PMMR imaging. This result will help in the optimization of scan parameters for PMMR imaging, which we are investigating. 18,19 Three major reasons are considered for this difference in MR relaxation times. The first is the increased water content of tissue. Katayama and associates reported the time-course increase of the water component of the brain using animal models of complete ischemia created by removing the hearts of rats. 20 This is attributed to increased lactic acid as a result of anaerobic glycolysis and increased osmotic pressure due to an increased number of proteins caused by autolysis in the ischemic brain, which results in the absorption of spinal fluid around the brain. 21–23 When the water content of brain tissue increases, T 1 and T 2 values of the brain increase. 24 –26 The second reason is a reduction of pH. The increase of lactic acid induces acidosis of the brain and resultant pH reduction. 27,28 Investigating the
livers of rats, Moser’s group reported that reduction of pH caused prolongation of T 2 values; they did not mention T 1 values. 29 We consider that pH reduction in the postmortem human brain can cause prolongation of T 2 values. The third reason is cooling of the body after death and subsequent storage of the cadaver in a refrigerator. The Bloembergen-Purcell-Pound theory states that the changes in T 1 and T 2 values are related to temperature change. 30 Reporting findings of their in vitro study, Nelson and Tung observed the linear shortening of T 1 values in the temperature range from 20 to 50°C in accordance with the reduction of temperature in CuSO 4 solutions, oils, tissue-simulating solutions (5% bovine serum albumin, 10% liposyn, 95% ethyl alcohol), and the white and yolk of an egg. 31 They noted that T 2 values were stable irrespective of temperature reduction in tissue-simulating solutions and the white and yolk of an egg. 31 In the temperature range from 4 to 37°C, Birkl and colleagues reported a linear decrease in the T 1 values of resected brain in accordance with the reduction of temperature, although T 2 values were stable irrespective of temperature reduction. 16 These reMagnetic Resonance in Medical Sciences
Cerebral MR Relaxation Time of the Dead
ports agree with our findings that T 1 values decreased in accordance with the reduction in body temperature but T 2 values were stable when body temperature ranged from 5 to 30°C. Regarding T 1 values, compared with MR imaging of living bodies, PMMR imaging of deceased bodies showed significantly shorter T1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe. This indicates that in the brain, the T 1 shortening effect due to low temperature is greater than the T 1 prolongation effect due to an increased water component. Regarding T 2 values, compared with findings of MR imaging in living subjects, PMMR imaging in our study showed significantly prolonged T 2 values in the gray matter and white matter of the frontal lobe, attributable to the increased water content and reduced pH of tissue. T 2 values of the caudate nucleus, putamen, and thalamus did not change significantly because of the deposition of ferritin, a paramagnetic substance. According to Curie’s law, the magnetic susceptibility of a paramagnetic substance is inversely proportional to the absolute temperature. 32 The increased magnetic susceptibility associated with temperature reduction induces changes in relaxation time. 33 Ferritin has a very weak T 1 shortening effect and strong T2 shortening effect. 34 Therefore, for the caudate nucleus, putamen, and thalamus, we consider that the T 2 prolongation effect due to an increased water component and reduced pH and the T 2 shortening effect due to ferritin at low temperature negated each other. Thayyil and colleagues reported that compared with findings of MR imaging in living subjects, findings from cerebral PMMR imaging in children showed longer T1 and T 2 values (time after death, 2.5 days, range, 2 to 5 days; axillary temperature, 7.4°C, range, 7.0 to 7.8°C). 14 Our findings of a tendency for shorter T 1 values and longer T 2 values differed from Thayyil’s results regarding T 1 values. We presume this difference is because their subjects were infants and ours were adults. The greater water content of brain tissue in children than adults 35,36 can be one reason for the age-dependent difference in RT 37 and explain the discrepancy between the results of Thayyil’s group and ours. Our study has 2 limitations. One is magnetic field strength. We conducted measurements using only a 1.5T MR imaging unit. RT depends on the magnetic field strength and may differ using imaging units of different strengths. Nonetheless, comparing the findings of MR imaging of the living subjects with those of PMMR imaging, we assert that the tendency of shortened T 1 and prolonged T 2 remains similar irrespective of the magnetic field strength. The secVol. 14 No. 1, 2015
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ond limitation is pH. Because we did not directly measure pH, we cannot define the degree of the acidosis effect on the T 2 values. Measurement of cerebral pH with an MR imaging system by chemical exchange saturation transfer imaging 38 will enable quantified measurement of the acidosis effect on T 2 values. In conclusion, compared with findings of cerebral MR imaging of living adult subjects, T 1 values tended to be shorter and T 2 values longer on PMMR imaging. The reasons for these phenomena include increased water content of tissue, reduced pH, and reduced body temperature after death. References 1.
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Brogdon BG. Research and applications of the new modalities. In: Brogdon BG, ed. Forensic Radiology. 1st ed. Boca Raton: CBC Press, 1998; 333–338. Swift B, Rutty GN. Recent advances in postmortem forensic radiology computed tomography and magnetic resonance imaging applications. In: Tsokos M, ed. Forensic Pathology Reviews. 1st ed. Totowa: Humana Press Inc, 2006; 355–404. Oesterhelweg L, Thali MJ. Experiences with virtual autopsy approach worldwide. In: Thali MJ, Dirnhofer R, Vock P, eds. The virtopsy approach. 1st ed. Boca Raton: CRC Press, 2009; 475–477. Roberts IS, Benamore RE, Benbow EW, et al. Postmortem imaging as an alternative to autopsy in the diagnosis of adult deaths: a validation study. Lancet 2012; 379:136–142. Takahashi N, Higuchi T, Shiotani M, et al. The effectiveness of postmortem multidetector computed tomography in the detection of fatal findings related to cause of non-traumatic death in the emergency department. Eur Radiol 2012; 22:152–160. Okuda T, Shiotani S, Sakamoto N, Kobayashi T. Background and current status of postmortem imaging in Japan: short history of ‘Autopsy imaging (Ai)’. Forensic Sci Int 2013; 225:3–8. Rutty GN, Brogdon G, Dedouit F, et al. Terminology used in publication for post-mortem cross-sectional imaging. Int J Legal Med 2013; 127:465– 466. Kobayashi T, Shiotani S, Kaga K, et al. Characteristic signal intensity changes on postmortem magnetic resonance imaging of the brain. Jpn J Radiol 2010; 28: 8–14. Kobayashi T, Isobe T, Shiotani S, et al. Postmortem magnetic resonance imaging dealing with low temperature objects. J Magn Reson Med Sci 2010; 9: 101–108. Ruder TD, Hatch GM, Siegenthaler L, et al. The influence of body temperature on image contrast in post mortem MRI. Eur J Radiol 2012; 81:1366–1370. Hart BL, Dudley MH, Zumwalt RE. Postmortem cranial MRI and autopsy correlation in suspected child abuse. Am J Forensic Med Pathol 1996; 17:217–224.
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Schmidt TM, Fischer R, Acar S, et al. DWI of the brain: postmortal DWI of the brain in comparison with in vivo data. Forensic Sci Int 2012; 10:180–183. Scheurer E, Lovblad KO, Kreis R, et al. Forensic application of postmortem diffusion weighted and diffusion tensor MR imaging of the human brain in situ. AJNR Am J Neuroradiol 2011; 32:1518–1524. Thayyil S, De Vita E, Sebire NJ, et al. Post-mortem cerebral magnetic resonance imaging T1 and T2 in fetuses, newborns and infants. Eur J Radiol 2012; 81: e232–e238. Shepherd TM, Flint JJ, Thelwall PE, et al. Postmortem interval alters the water relaxation and diffusion properties of rat nervous tissue–implications for MRI studies of human autopsy samples. Neuroimage 2009; 44:820 –826. Birkl C, Langkammer C, Haybaeck J, et al. Temperature-induced changes of magnetic resonance relaxation times in the human brain: a postmortem study. Magn Reson Med 2014; 71:1575–1580. Kobayashi T, Ookubo J, Monma M, et al. [Evaluation of measurement accuracy of a T1 and T2 mapping tool]. JJMRM 2012; 32:66–75. [Article in Japanese] Ruder TD, Thali MJ, Hatch GM. Essentials of forensic post-mortem MR imaging in adults. Br J Radiol 2014; 87:20130567. Kobayashi T, Monma M, Baba T, et al. Optimization of inversion time for postmortem short-tau inversion recovery (STIR) MR imaging. Magn Reson Med Sci 2014; 13:67–72. Katayama Y, Terashi A, Nagadumi A, et al. [Studies on production of cerebral edema in complete ischemia]. Myakukangaku [Angiology] 1984; 24:1271– 1274 [in Japanese]. Myers RE, Yamaguchi M. Effect of serum glucose concentration on brain response to circulatory arrest. J Neuropathol Exp Neurol 1976; 35:301. Yamaguchi M, Myers RE. Comparison of brain biochemical changes produced by anoxia and hypoxia. J Neuropathol Exp Neurol 1976; 35:302. Bandaranayake NM, Nemoto EM, Stezoski SW. Rat brain osmolality during barbiturate anesthesia and global brain ischemia. Stroke 1978; 9:249–254. Kiricuta IC Jr, Simplăceanu V. Tissue water content and nuclear magnetic resonance in normal and tumor tissues. Cancer Res 1975; 35:1164–1167. Araki T, Inouye T, Suzuki H, Machida T, Iio M. Magnetic resonance imaging of brain tumors: measurement of T1. Work in Progress. Radiology 1984; 150: 95–98.
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Kamman RL, Go KG, Brouwer W, Berendsen HJ. Nuclear magnetic resonance relaxation in experimental brain edema: effects of water concentration, protein concentration, and temperature. Magn Reson Med 1988; 6:265–274. Hardy JA, Wester P, Winblad B, Gezelius C, Bring G, Eriksson A. The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue. J Neural Transm 1985; 61:253–264. Kohno K, Hoehn-Berlage M, Mies G, Back T, Hossmann KA. Relationship between diffusionweighted MR images, cerebral blood flow, and energy state in experimental brain infarction. Magn Reson Imaging 1995; 13:73–80. Moser E, Winklmayr E, Holzmüller P, Krssak M. Temperature- and pH-dependence of proton relaxation rates in rat liver tissue. Magn Reson Imaging 1995; 13:429– 440. Bloembergen N, Purcell EM, Pound RV. Relaxation effects in nuclear magnetic resonance absorption. Physiol Rev 1948; 73:679–712. Nelson TR, Tung SM. Temperature dependence of proton relaxation times in vitro. Magn Reson Med 1987; 5:189–199. Rieke V, Butts Pauly K. MR Thermometry. J Magn Reson Imaging 2008; 27:376–390. Lotfipour AK, Wharton S, Schwarz ST, et al. High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson’s disease. J Magn Reson Imaging 2012; 35:48–55. Vymazal J, Righini A, Brooks RA, et al. T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 1999; 211:489– 495. Barkovich AJ, Raybaud C. Pediatric Neuroimaging 5th ed. 2011; 1–19. Barkovich AJ, Kjos BO, Jackson DE Jr, Norman D. Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T. Radiology 1988; 166(1 Pt 1): 173–180. Breger RK, Yetkin FZ, Fischer ME, Papke RA, Haughton VM, Rimm AA. T1 and T2 in the cerebrum: correlation with age, gender, and demographic factors. Radiology 1991; 181:545–547. Zhou J, Payen JF, Wilson DA, Traystman RJ, van Zijl PC. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 2003; 9:1085–1090.
Magnetic Resonance in Medical Sciences
doi:10.2463/mrms.2013-0126
© 2014 Japanese Society for Magnetic Resonance in Medicine
MAJOR PAPER
Cerebral Relaxation Times from Postmortem MR Imaging of Adults Kazuya TASHIRO1*, Seiji SHIOTANI2, Tomoya KOBAYASHI1, Kazunori KAGA1, Hajime SAITO1, Satoka SOMEYA1, Katsumi MIYAMOTO1, and Hideyuki HAYAKAWA3 1
Department of Radiological Technology, Tsukuba Medical Center Hospital 1–3–1 Amakubo, Tsukuba, Ibaraki 305–8558, Japan 2 Department of Radiology, Tsukuba Medical Center Hospital 3 Department of Forensic Medicine, Tsukuba Medical Examiner’s Office (Received December 13, 2013; Accepted July 16, 2014; published online December 15, 2014)
Purpose: We measured T 1 and T 2 values of cerebral postmortem magnetic resonance (PMMR) imaging and compared the data of cadavers with that of living human subjects. Materials and Methods: We performed PMMR imaging of the brains of 30 adults (22 men, 8 women; mean age, 58.2 years) whose deaths were for reasons other than brain injury or disease at a mean of 29.4 hours after death. Before imaging, the bodies were kept in cold storage at 4°C (mean rectal temperature, 15.6°C). We measured T 1 and T 2 values in the brain bilaterally at 5 sites (bilateral caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe) and compared the data of PMMR imaging with that from MR imaging of the corresponding sites in 24 healthy volunteers (9 men, 15 women; mean age, 51.8 years). We also investigated the influence of body temperature on T 1 and T 2 values. Results: Compared with MR imaging findings in the living subjects, PMMR imaging showed significantly shorter T 1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe and significantly longer T 2 values in the gray matter and white matter of the frontal lobe; T 2 values in the caudate nucleus, putamen, and thalamus showed no such differences. T 1 values correlated significantly with body temperature in all 5 brain sites measured, but T 2 values did not. Conclusion: Compared with findings of cerebral MR imaging in living adult subjects, those of PMMR imaging tended to demonstrate shorter T 1 values and longer T 2 values. We attribute this to increased water content of tissue, reduced pH, and reduced body temperature after death. Keywords: brain, in vivo, low body temperature, postmortem cross-sectional imaging, postmortem magnetic resonance imaging (PMMR imaging) imaging findings require analyses of quantified data. Several papers have described PMMR imaging findings in the brain, 8,11–14 and PMMR imaging and ADC values of the adult brain,12,13 T 1 and T 2 values of the pediatric brain, 14 and T 1 and T 2 values of the rat and human adult brain in vitro have been reported. 15,16 However, we believe there are no published data regarding quantitative T 1 and T 2 values in vivo of cerebral PMMR imaging of adults. Herein, we report the T 1 and T 2 values of cerebral MR imaging of deceased adults and compare them with those of living adult subjects.
Introduction The worldwide decline in the rate of conventional autopsies has led to the need for and frequency of postmortem imaging as a complementary, supplementary, or alternative method for autopsy.1–7 Postmortem magnetic resonance (PMMR) imaging has shown that MR signals and image contrast change after death. 8 –10 Optimization of parameters for PMMR imaging and accurate interpretation of *Corresponding author, Phone: +81-29-851-3511, Fax: +8129-858-2773, E-mail: [email protected] 51
52
Materials and Methods Subjects We examined PMMR imaging data of 30 adults (22 men, 8 women; aged 26 to 96 years, mean 58.2 years) who died suddenly and unexpectedly and had no abnormal results of neuropathological examination of the brain. Their bodies were kept in cold storage at 4°C and subjected to PMMR imaging 12 to 96 hours after confirmation of death (mean 29.4 hours). Their rectal temperatures, measured immediately after PMMR imaging with an industrial thermometer (7-257-01, AS ONE, Osaka, Japan) were 5 to 30°C (mean 15.6°C). Autopsy was performed on each subject after PMMR imaging. Causes of death were 5 cases each of ischemic heart disease, suffocation, and acute heart failure, 3 cases of drowning in the bathtub; 2 cases each of malnutrition, acute drug intoxication, cervical spine injury, and acute alcohol intoxication, and one case each of hemorrhagic gastric ulcer, diabetic ketoacidosis, traumatic rupture of the aorta, and ileus. For comparison, we also examined MR imaging data of 24 healthy volunteers (9 men, 15 women; aged 43 to 79 years, mean 51.8 years) who gave written informed consent to participate in our study. None of these subjects had intracranial morphological abnormalities on MR imaging, neurological disease, history of severe head trauma, or psychiatric disorder. Mean age did not differ significantly between the deceased and living subjects. Scan conditions With the permission of our institutional ethics committee, we performed PMMR imaging and MR imaging of volunteers using the same 1.5-tesla MR imaging clinical scanner (Avanto, Siemens, Erlangen, Germany) with a dedicated 12-element phased-array head coil. We measured T 1 and T 2 values with a relaxation time (RT) map creation tool (syngo MapIt, Siemens, Erlangen, Germany). 17 Table 1 shows the scan parameters for the brain. Analyses A radiological technologist (K.T.) with 5 years of experience defined circular regions of interest (ROIs) of 5 mm 2 in the brain bilaterally in the caudate nucleus, putamen, thalamus and gray matter and white matter in the frontal lobes at the level of the basal ganglia (Fig. 1). Statistical analyses were performed using statistical software (Excel 2010, Microsoft, Redmond, WA, USA) with Statcel 2 (OMS, Tokyo, Japan) add-in software. Parametric statistics (arithmetic
K. Tashiro et al.
Table 1. Scan parameters of postmortem magnetic resonance (PMMR) imaging based on the syngo MapIt method (Siemens Medical Systems, Erlangen, Germany) Scan parameters
T1 map
T2 map
TR/TE (ms)
15/1.86
2000/30, 60, 90, 120, 150 180° 4/0.8 0.86 © 0.86 220 4.6 11
Flip angle Slice thickness/gap (mm) Matrix size (mm) Field of view (FOV) (mm) Scanning time (min) Number of slices
5°, 26° 3/0 0.86 © 0.86 220 2.7 22 (3D)
TE, echo time; TR, repetition time; 3D, 3-dimensional
Fig. 1. Regions of interest (ROIs) placed at the level of the basal ganglia on postmortem magnetic resonance (MR) images. ROIs were placed bilaterally on the 1) caudate nucleus, 2) putamen, 3) thalamus, 4) frontal gray matter, and 5) frontal white matter.
mean value « standard deviation [SD]) and Student’s t test were used with a significance value of p < 0.05 for group differences. We compared measured RT values between the deceased and living subjects and investigated the extent of the influence of differences in rectal temperature on T 1 and T 2 values. The relationships among T 1 values, T2 values, and rectal temperatures were statistically analyzed with Pearson’s correlation coefficient using the least squares method.
Magnetic Resonance in Medical Sciences
Cerebral MR Relaxation Time of the Dead
Results We observed no specific abnormality, except for signal intensity and contrast, between cerebral PMMR imaging and MR imaging of living subjects. T 1 and T 2 values did not differ significantly between the bilateral hemispheres (p Ú 0.05), so we averaged values from both hemispheres. Table 2 shows mean T 1 and T 2 values for the adult brain. Compared with the cerebral MR imaging of the living subjects, PMMR imaging showed significantly shorter T 1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe. T 2 values were significantly longer in the gray matter and white matter of the frontal lobe, but no such significant differences were found in the caudate nucleus, putamen, and thalamus. With PMMR imaging, T 1 values correlated significantly with rectal temperature for the 5 sites of the brain measured (Fig. 2a–e), but T 2 values did not (Fig. 3a–e).
53
Table 2. Differences in relaxation time on magnetic resonance (MR) imaging between postmortem and living bodies
Caudate nucleus Putamen Thalamus Frontal gray matter Frontal white matter
T1 [ms]
T2 [ms]
Postmortem (Living body)
Postmortem (Living body)
955 « 104 (1250 « 81)* 855 « 100 (1126 « 54)* 740 « 74 (1230 « 74)* 935 « 88 (1209 « 94)* 623 « 56 (707 « 40)*
84.1 « 6.2 (86.5 « 2.4) 74.5 « 7.3 (73.7 « 3.2) 82.7 « 6.1 (82.0 « 3.3) 116.8 « 11.2 (95.4 « 6.1)* 96.1 « 5.9 (78.1 « 3.0)*
*indicates statistically significant difference between postmortem and living bodies
Fig. 2. Relationship between T 1 values and rectal temperatures of deceased subjects in the a) caudate nucleus, b) putamen, c) thalamus, d) frontal gray matter, and e) frontal white matter. Vol. 14 No. 1, 2015
54
K. Tashiro et al.
Fig. 3. Relationship between T2 values and rectal temperature of deceased subjects in the a) caudate nucleus, b) putamen, c) thalamus, d) frontal gray matter, and e) frontal white matter.
Discussion Compared with the findings of cerebral MR imaging of living subjects, T 1 values tended to be shorter and T 2 values prolonged on PMMR imaging. This result will help in the optimization of scan parameters for PMMR imaging, which we are investigating. 18,19 Three major reasons are considered for this difference in MR relaxation times. The first is the increased water content of tissue. Katayama and associates reported the time-course increase of the water component of the brain using animal models of complete ischemia created by removing the hearts of rats. 20 This is attributed to increased lactic acid as a result of anaerobic glycolysis and increased osmotic pressure due to an increased number of proteins caused by autolysis in the ischemic brain, which results in the absorption of spinal fluid around the brain. 21–23 When the water content of brain tissue increases, T 1 and T 2 values of the brain increase. 24 –26 The second reason is a reduction of pH. The increase of lactic acid induces acidosis of the brain and resultant pH reduction. 27,28 Investigating the
livers of rats, Moser’s group reported that reduction of pH caused prolongation of T 2 values; they did not mention T 1 values. 29 We consider that pH reduction in the postmortem human brain can cause prolongation of T 2 values. The third reason is cooling of the body after death and subsequent storage of the cadaver in a refrigerator. The Bloembergen-Purcell-Pound theory states that the changes in T 1 and T 2 values are related to temperature change. 30 Reporting findings of their in vitro study, Nelson and Tung observed the linear shortening of T 1 values in the temperature range from 20 to 50°C in accordance with the reduction of temperature in CuSO 4 solutions, oils, tissue-simulating solutions (5% bovine serum albumin, 10% liposyn, 95% ethyl alcohol), and the white and yolk of an egg. 31 They noted that T 2 values were stable irrespective of temperature reduction in tissue-simulating solutions and the white and yolk of an egg. 31 In the temperature range from 4 to 37°C, Birkl and colleagues reported a linear decrease in the T 1 values of resected brain in accordance with the reduction of temperature, although T 2 values were stable irrespective of temperature reduction. 16 These reMagnetic Resonance in Medical Sciences
Cerebral MR Relaxation Time of the Dead
ports agree with our findings that T 1 values decreased in accordance with the reduction in body temperature but T 2 values were stable when body temperature ranged from 5 to 30°C. Regarding T 1 values, compared with MR imaging of living bodies, PMMR imaging of deceased bodies showed significantly shorter T1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe. This indicates that in the brain, the T 1 shortening effect due to low temperature is greater than the T 1 prolongation effect due to an increased water component. Regarding T 2 values, compared with findings of MR imaging in living subjects, PMMR imaging in our study showed significantly prolonged T 2 values in the gray matter and white matter of the frontal lobe, attributable to the increased water content and reduced pH of tissue. T 2 values of the caudate nucleus, putamen, and thalamus did not change significantly because of the deposition of ferritin, a paramagnetic substance. According to Curie’s law, the magnetic susceptibility of a paramagnetic substance is inversely proportional to the absolute temperature. 32 The increased magnetic susceptibility associated with temperature reduction induces changes in relaxation time. 33 Ferritin has a very weak T 1 shortening effect and strong T2 shortening effect. 34 Therefore, for the caudate nucleus, putamen, and thalamus, we consider that the T 2 prolongation effect due to an increased water component and reduced pH and the T 2 shortening effect due to ferritin at low temperature negated each other. Thayyil and colleagues reported that compared with findings of MR imaging in living subjects, findings from cerebral PMMR imaging in children showed longer T1 and T 2 values (time after death, 2.5 days, range, 2 to 5 days; axillary temperature, 7.4°C, range, 7.0 to 7.8°C). 14 Our findings of a tendency for shorter T 1 values and longer T 2 values differed from Thayyil’s results regarding T 1 values. We presume this difference is because their subjects were infants and ours were adults. The greater water content of brain tissue in children than adults 35,36 can be one reason for the age-dependent difference in RT 37 and explain the discrepancy between the results of Thayyil’s group and ours. Our study has 2 limitations. One is magnetic field strength. We conducted measurements using only a 1.5T MR imaging unit. RT depends on the magnetic field strength and may differ using imaging units of different strengths. Nonetheless, comparing the findings of MR imaging of the living subjects with those of PMMR imaging, we assert that the tendency of shortened T 1 and prolonged T 2 remains similar irrespective of the magnetic field strength. The secVol. 14 No. 1, 2015
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ond limitation is pH. Because we did not directly measure pH, we cannot define the degree of the acidosis effect on the T 2 values. Measurement of cerebral pH with an MR imaging system by chemical exchange saturation transfer imaging 38 will enable quantified measurement of the acidosis effect on T 2 values. In conclusion, compared with findings of cerebral MR imaging of living adult subjects, T 1 values tended to be shorter and T 2 values longer on PMMR imaging. The reasons for these phenomena include increased water content of tissue, reduced pH, and reduced body temperature after death. References 1.
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