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Evaluation of thymic volume by postmortem computed tomography
Legal Medicine 17 (2015) 251–254
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Evaluation of thymic volume by postmortem computed tomography Shuntaro Abe a,b,c,⇑, Iwao Hasegawa a,c, Hermann Vogel a, Axel Heinemann a, Koichi Suzuki b, Klaus Püschel a a
Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, Germany Division of Preventive & Social Medicine, Department of Legal Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, Japan c Tokyo Medical Examiner’s Office, Tokyo Metropolitan Government, 4-21-18 Otsuka, Bunkyo-ku, Tokyo, Japan b
a r t i c l e
i n f o
Article history: Received 6 February 2015 Received in revised form 23 February 2015 Accepted 23 February 2015 Available online 3 March 2015 Keywords: Thymic involution Child abuse Postmortem computed tomography Forensic autopsy
a b s t r a c t The thymus is exceedingly sensitive to stress and undergoes abrupt involution as a result of exposure to strong stress in early childhood. Therefore, thymic involution is often utilized to assess the presence of a stressful environment, such as an environment involving child abuse, in forensic medicine. In recent years, computed tomography (CT) has been commonly used in the daily practice of forensic medicine. We have focused on the thymic volume in postmortem CT images to evaluate the presence of a stressful antemortem environment. We calculated the thymus volume from postmortem CT images of children under six years old and demonstrated that the volume showed a positive correlation with the real weight obtained from an autopsy. The evaluation of thymic volume by CT may make it possible for us to identify child maltreatment. The most useful feature of this application of CT is to be able to demonstrate thymic involution less invasively in a surviving victim. Ó 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The thymus is located in the anterior mediastinum. It is a primary lymphoid organ that is critical for the differentiation of Tcells and for the development of T-cell-mediated immunity in childhood. The thymus markedly increases in volume in early childhood and is physiologically involuted after puberty. The thymus exhibits acute involution as a result of exposure to strong and/or long-term stress in childhood [1,2]. A large amount of serum glucocorticoid may induce naïve T-cell apoptosis in the thymic cortex [3], resulting in acute thymic involution. Therefore, thymic involution has been utilized in forensic autopsies to evaluate the degree and duration of child abuse/neglect [2,4]. Diagnostic imaging, especially computed tomography (CT), is now commonly used in forensic medicine. CT provides whole body imaging and is a quick and convenient method of organ volume measurement. Few reports on the evaluation of thymic volume on CT are available, however. In the present study, we determined the thymic volume in children using postmortem CT (PMCT) imaging and compared this volume with that determined in autopsy ⇑ Corresponding author at: Division of Preventive & Social Medicine, Department of Legal Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. Tel.: +81 72 683 1221x2642; fax: +81 72 684 6515. E-mail address: [email protected] (S. Abe). http://dx.doi.org/10.1016/j.legalmed.2015.02.006 1344-6223/Ó 2015 Elsevier Ireland Ltd. All rights reserved.
findings. This is the first report describing autopsy findings and PMCT findings regarding the thymus. 2. Materials and methods Thymic volume and weight were compared in 27 cases (0– 6 years old) autopsied in the Department of Legal Medicine at the University Medical Center Hamburg-Eppendorf (Table 1). Among these cases, a single case (No. 17) was suspected to involve child abuse. Whole body CT scans were performed using a PHILIPS MX8000 Quad CT scanner. Image data were handled using OsiriX imaging software run on a Macintosh computer (Version 3.9.4. http:// www.osirix-viewer.com/, version 6.0 is now available on the website). The thymic volume was calculated in each case from the region of interest (ROI). The thymic region was bordered by a green line as shown in Fig. 1a and b. Images were displayed using brain settings; window width = 100 Hounsfield units (HU); window level = 50 HU. All cases examined in the present study showed good resolution, and the postmortem periods were four days or less. ROIs were placed on the thymus images using the ‘‘mouse button function’’ tool at 10-mm intervals. Missing ROIs among the manually placed ROIs were filled in using the ‘‘create missing ROI’’ command. The ROIs were placed under the supervision of a radiologist. Finally,
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S. Abe et al. / Legal Medicine 17 (2015) 251–254
Table 1 Overview of cases. No.
Age in days
Sex
Cause of death
Group
Body weight (g)
Height (cm)
Volume of thymus (cm3)
CT attenuation value (HU)
Weight of thymus (g)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
18 41 44 48 51 69 88 89 96 128 129 136 139 176 210 261 299 351 374 398 556 563 570 705 795 1509 1881
M F M F W F F F M M M M M F M M F M M M F M M M M M F
Suspicion of SIDS Suspicion of SIDS Inflammatory heart disease Unclear Unclear Suspicion of SIDS Unclear Unclear Suspicion of SIDS Congenital heart disease Unclear Respiratory infection Suspicion of SIDS Suspicion of SIDS Unclear Suspicion of SIDS Suspicion of child abuse Suspicion of SIDS Respiratory infection Head injury Intestinal volvulus Unclear Foreign body aspiration Drowning Head injury Unclear Unclear
SIDS SIDS Disease Unclear Unclear SIDS Unclear Unclear SIDS Disease Unclear Disease SIDS SIDS Unclear SIDS Abuse SIDS Disease Accident Disease Unclear Accident Accident Accident Unclear Unclear
4048 4092 3520 5000 4226 5136 6100 6300 5600 6400 5490 7000 7400 4900 6500 9900 4802 9300 9600 12,100 9900 10,200 15,400 13,700 15,000 18,000 22,500
54.5 57.0 52.0 54.0 58.0 62.0 56.0 63.0 60.0 64.0 60.0 70.0 66.0 70.0 61.0 71.0 66.0 78.0 78.0 82.0 79.0 75.0 82.0 87.0 83.0 108.0 119.0
11.2 9.0 18.8 14.9 13.9 35.6 15.1 20.5 30.4 23.6 20.0 10.9 24.9 54.6 46.7 18.8 5.3 40.7 25.6 17.6 22.6 17.8 24.0 27.8 18.8 17.8 36.0
76.3 66.4 59.7 59.2 52.8 71.1 53.1 61.9 60.9 68.5 65.1 57.2 71.5 56.9 59.9 70.4 60.8 61.3 69.5 78.8 68.1 73.7 72.7 67.4 72.2 73.7 64.7
13 17 25 21 18 43 18 25 40 29 25 18 34 68 48 31 7 55 35 30 23 24 25 36 17 29 54
Abbreviation: SIDS, sudden infant death syndrome.
the volume and mean CT attenuation values were obtained using the ‘‘compute volume’’ command. Each subject’s age in days, height (cm), body weight (g), thymic weight (g) and cause of death were obtained from the autopsy records. This study was performed in accordance with the laws of the city of the Hamburg and the data production and ethical guidelines of the University Medical Center Hamburg-Eppendorf. The authors have no conflict of interest directly relevant to the content of this article. 3. Results
Fig. 1. Horizontal sections of the thymus on CT images taken at the level of the carina. The green line indicates the thymic border and a region of interest. (a) A 10month-old female with thymic involution (Case No. 17 in Table 1). (b) A 12-monthold male without thymic involution (Case No. 18).
The thymic volume and CT attenuation values in all cases examined are summarized in Table 1. The relation between thymic weight and volume was investigated using Pearson’s correlation coefficient test. A statistically significant (p < 0.001) strong correlation (r = 0.95) was observed between thymic weight and volume (Fig. 2). Case No. 17, who was suspected to be a victim of child abuse, presented obvious thymic involution, e.g., thinning of the thickness in a horizontal section on the CT image (Fig. 1a). On the other hand, case No. 18, in which the cause of death seemed to be sudden infant death syndrome (SIDS), did not show thymic involution. A non-involuted thymus shows its thickest slice thickness on the horizontal section at the level of the carina. The involuted thymus in case No. 17 shows thinning but exhibits a roughly rectangular structure on the horizontal section, as in the non-involuted thymus in case No. 18. Fig. 3 shows three-dimensional (3D) images of the thymuses of cases No. 17 (a–c) and No. 18 (d–f). These figures visualize the thickness of the thymus well. The CT attenuation value did not correlate with body height, body weight, thymic volume, thymic weight, or postmortem period.
S. Abe et al. / Legal Medicine 17 (2015) 251–254
Fig. 2. Correlation between thymic weight and volume. r = 0.95, p < 0.001. Weight (g) = 3.072 + 1.164 Volume (cm3). The relation was investigated using Pearson’s correlation coefficient test. The black arrow identifies Case No. 17 with thymic involution.
4. Discussion Thymic volume and weight were well correlated, as shown in Fig. 2. Therefore, thymic weight can be calculated from thymic volume estimates obtained from CT images. The thymic weight calculated from the thymic volume could be compared with the normal thymic weight or with past autopsy reports of cases with thymic involution. The case in which child abuse was suspected showed thymic involution (Figs. 1 and 3), as was also shown in a previous report [2]. A 3D reconstruction of the thymus clearly demonstrates thymic involution (Fig. 3a–c). Although the frontal view of the involuted thymus shows no difference in shape on the 3D images, the thickness was markedly decreased. These 3D images were readily obtainable from CT images by rendering, allowing the thymic involution to be visualized clearly.
253
The thickness of the thymus is a good, single-glance indicator of thymic involution. The thickest slice is generally obtained at the level of the carina on horizontal sections, and thus this slice level is adequate as an initial step in a screening test. The thymic volume and CT attenuation value are not correlated with the postmortem period. Those images that were scanned more than five days after death were excluded from the analysis since the thymic borders were difficult to detect. Extremely lowresolution images were not suitable for this analysis. The scan condition should be examined for children with small bodies in order to detect the thymic border correctly. Furthermore, mediastinum lesions such as hemorrhages caused by cardiac compression might obscure the thymic border on CT images. Mediastinum lesions are always considered in order to obtain an accurate assessment of the border. We considered a 10-mm slice thickness to be the minimum requirement in this method. Breiman et al. compared the spleen volume measured on CT images to that measured after surgical resection, and they reported that the mean percentage error in detecting the spleen volume using the sum-of-areas technique was 3.59% at a 10-mm scan spacing [5] This error rate is considered to be adequate. No differences in volume were observed between those calculated using scans semi-automatically set at 10-mm intervals and those manually set at different intervals (<10 mm) on all slice sections. Thymic volume evaluation was applicable only in prepubescent cases because of the pubertal onset of age-related physiological thymic involution. The adult thymus with age-related involution shows a triangular structure on CT images [6,7]. An involuted thymus in childhood, however, maintains a rectangular structure; i.e., it differs significantly in shape from age-related physiological involution. The thymus is morphologically fixed by connective tissues in the mediastinum; when rapid involution of the thymus occurs due to stress, the shape of the thymus maintains its rectangular structure in CT images. The key advantage of evaluating thymic volume by CT scan is to be able to demonstrate thymic involution less invasively in a surviving victim. The evaluation of thymic volume may help pediatricians, psychiatrists, and other health professionals in hospitals to recognize child maltreatment and allow them to intervene at an early stage.
Fig. 3. The 3D images of the thymus obtained from CT images by rendering. (a–c) Case No. 17 with thymic involution. (d–f) Case No. 18 without thymic involution. The 3D images visualize the thickness of the thymus well.
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S. Abe et al. / Legal Medicine 17 (2015) 251–254
The detection of child maltreatment without obvious findings, such as injuries, growth retardation, mental problems, etc., is very difficult. Thymic volume evaluation may provide an opportunity to recognize cases of psychological abuse and/or neglect without specific findings at an early stage. Thus, we believe that the volume of the thymus should be evaluated as routinely as possible in neonates, infants, and children in cases in which child maltreatment is suspected. Ultrasonography is a common diagnostic imaging method and should be the first-choice examination for living victims because it is much less invasive than other methods. It should be noted that performing thymic ultrasonography requires a certain level of proficiency. In the future, 3D ultrasonography may be efficacious for thymic volume evaluation. Prodhomme et al. reported that the virtual volume obtained using magnetic resonance imaging (MRI) was scarcely different from the real volume measured by the water replacement method at autopsy [8]. MRI is a promising imaging method, but it is not yet generally available in forensic medicine. Stress-induced thymic involution will not only occur in cases of child maltreatment; it can also be caused by bacterial infection [9], viral infection (especially HIV [10]), ionizing radiation [11], restraint, starvation [12], or chemotherapy [13]. Meanwhile, myasthenia gravis and hyperthyroidism may induce thymic hyperplasia [14,15]. These anamneses and thymus neoplasms should be investigated carefully to assess the causes of thymic volume abnormalities. Physiological thymic involution seldom occurs in early childhood; the screening test for thymic involution must be exploited for disclosing child maltreatment. In conclusion, we revealed that thymic volume and weight were well correlated. CT is valuable for detecting the presence of stressful environments in childhood. Further investigation is needed to reveal what specific stressful environments could be related to thymic findings. Clinical CT images could be used to investigate thymic volume changes in surviving victims. The comparison of postmortem microscopic investigations with CT findings should be performed to reveal the correlations between histological structure and CT findings with regard to the thymus, particularly in terms of the CT attenuation value. Additional research should improve the accuracy and usability of this method.
Acknowledgement This research is supported by the Institutional Program for Young Researcher Overseas Visits (Japan Society for the Promotion of Science). References [1] Selye H. Stress and disease. Science 1955;122:625–31. [2] Fukunaga T, Mizoi Y, Yamashita A, Yamada M, Yamamoto Y, Tatsuno Y, et al. Thymus of abused/neglected children. Forensic Sci Int 1992;53:69–79. [3] Tarcic N, Ovadia H, Weiss DW, Weidenfeld J. Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids. J Neuroimmunol 1998;82:40–6. [4] Tanegashima A, Yamamoto H, Yada I, Fukunaga T. Estimation of stress in child neglect from thymic involution. Forensic Sci Int 1999;101:55–63. [5] Breiman RS, Beck JW, Korobkin M, Glenny R, Akwari OE, Heaston DK, et al. Volume determinations using computed tomography. AJR Am J Roentgenol 1982;138:329–33. http://dx.doi.org/10.2214/ajr.138.2.329. [6] Nishino M, Ashiku SK, Kocher ON, Thurer RL, Boiselle PM, Hatabu H. The thymus: a comprehensive review. Radiographics 2006;26:335–48. http:// dx.doi.org/10.1148/rg.262045213. [7] Bogot NR, Quint LE. Imaging of thymic disorders. Cancer Imaging 2005;5:139–49. http://dx.doi.org/10.1102/1470-7330.2005.0107. [8] Prodhomme O, Seguret F, Martrille L, Pidoux O, Cambonie G, Couture A, et al. Organ volume measurements: comparison between MRI and autopsy findings in infants following sudden unexpected death. Arch Dis Child Fetal Neonatal Ed 2012:434–9. http://dx.doi.org/10.1136/fetalneonatal-2011-301309. [9] Senati M, Polacco M, Grassi VM, Carbone A, De-Giorgio F. Child abuse followed by fatal systemic Pseudomonas aeruginosa infection. Leg Med (Tokyo) 2013;15:28–31. http://dx.doi.org/10.1016/j.legalmed.2012.08.001. [10] Ye P, Kirschner DE, Kourtis AP. The thymus during HIV disease: role in pathogenesis and in immune recovery. Curr HIV Res 2004;2:177–83. [11] Gruver AL, Sempowski GD. Cytokines, leptin, and stress-induced thymic atrophy. J Leukoc Biol 2008;84:915–23. http://dx.doi.org/10.1189/jlb.0108025. [12] Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr 1997;66:460S–3S. [13] Choyke PL, Zeman RK, Gootenberg JE, Greenberg JN, Hoffer F, Frank JA. Thymic atrophy and regrowth in response to chemotherapy: CT evaluation. Am J Roentgenol 1987;149:269–72. [14] Inaoka T, Takahashi K, Mineta M, Yamada T, Shuke N, Okizaki A, et al. Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging. Radiology 2007;243:869–76. http://dx.doi.org/10.1148/ radiol.2433060797. [15] Raica M, Cîmpean AM, Encica˘ S, Cornea R. Involution of the thymus: a possible diagnostic pitfall. Rom J Morphol Embryol 2007;48:101–6.
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Evaluation of thymic volume by postmortem computed tomography Shuntaro Abe a,b,c,⇑, Iwao Hasegawa a,c, Hermann Vogel a, Axel Heinemann a, Koichi Suzuki b, Klaus Püschel a a
Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, Germany Division of Preventive & Social Medicine, Department of Legal Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, Japan c Tokyo Medical Examiner’s Office, Tokyo Metropolitan Government, 4-21-18 Otsuka, Bunkyo-ku, Tokyo, Japan b
a r t i c l e
i n f o
Article history: Received 6 February 2015 Received in revised form 23 February 2015 Accepted 23 February 2015 Available online 3 March 2015 Keywords: Thymic involution Child abuse Postmortem computed tomography Forensic autopsy
a b s t r a c t The thymus is exceedingly sensitive to stress and undergoes abrupt involution as a result of exposure to strong stress in early childhood. Therefore, thymic involution is often utilized to assess the presence of a stressful environment, such as an environment involving child abuse, in forensic medicine. In recent years, computed tomography (CT) has been commonly used in the daily practice of forensic medicine. We have focused on the thymic volume in postmortem CT images to evaluate the presence of a stressful antemortem environment. We calculated the thymus volume from postmortem CT images of children under six years old and demonstrated that the volume showed a positive correlation with the real weight obtained from an autopsy. The evaluation of thymic volume by CT may make it possible for us to identify child maltreatment. The most useful feature of this application of CT is to be able to demonstrate thymic involution less invasively in a surviving victim. Ó 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The thymus is located in the anterior mediastinum. It is a primary lymphoid organ that is critical for the differentiation of Tcells and for the development of T-cell-mediated immunity in childhood. The thymus markedly increases in volume in early childhood and is physiologically involuted after puberty. The thymus exhibits acute involution as a result of exposure to strong and/or long-term stress in childhood [1,2]. A large amount of serum glucocorticoid may induce naïve T-cell apoptosis in the thymic cortex [3], resulting in acute thymic involution. Therefore, thymic involution has been utilized in forensic autopsies to evaluate the degree and duration of child abuse/neglect [2,4]. Diagnostic imaging, especially computed tomography (CT), is now commonly used in forensic medicine. CT provides whole body imaging and is a quick and convenient method of organ volume measurement. Few reports on the evaluation of thymic volume on CT are available, however. In the present study, we determined the thymic volume in children using postmortem CT (PMCT) imaging and compared this volume with that determined in autopsy ⇑ Corresponding author at: Division of Preventive & Social Medicine, Department of Legal Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. Tel.: +81 72 683 1221x2642; fax: +81 72 684 6515. E-mail address: [email protected] (S. Abe). http://dx.doi.org/10.1016/j.legalmed.2015.02.006 1344-6223/Ó 2015 Elsevier Ireland Ltd. All rights reserved.
findings. This is the first report describing autopsy findings and PMCT findings regarding the thymus. 2. Materials and methods Thymic volume and weight were compared in 27 cases (0– 6 years old) autopsied in the Department of Legal Medicine at the University Medical Center Hamburg-Eppendorf (Table 1). Among these cases, a single case (No. 17) was suspected to involve child abuse. Whole body CT scans were performed using a PHILIPS MX8000 Quad CT scanner. Image data were handled using OsiriX imaging software run on a Macintosh computer (Version 3.9.4. http:// www.osirix-viewer.com/, version 6.0 is now available on the website). The thymic volume was calculated in each case from the region of interest (ROI). The thymic region was bordered by a green line as shown in Fig. 1a and b. Images were displayed using brain settings; window width = 100 Hounsfield units (HU); window level = 50 HU. All cases examined in the present study showed good resolution, and the postmortem periods were four days or less. ROIs were placed on the thymus images using the ‘‘mouse button function’’ tool at 10-mm intervals. Missing ROIs among the manually placed ROIs were filled in using the ‘‘create missing ROI’’ command. The ROIs were placed under the supervision of a radiologist. Finally,
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S. Abe et al. / Legal Medicine 17 (2015) 251–254
Table 1 Overview of cases. No.
Age in days
Sex
Cause of death
Group
Body weight (g)
Height (cm)
Volume of thymus (cm3)
CT attenuation value (HU)
Weight of thymus (g)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
18 41 44 48 51 69 88 89 96 128 129 136 139 176 210 261 299 351 374 398 556 563 570 705 795 1509 1881
M F M F W F F F M M M M M F M M F M M M F M M M M M F
Suspicion of SIDS Suspicion of SIDS Inflammatory heart disease Unclear Unclear Suspicion of SIDS Unclear Unclear Suspicion of SIDS Congenital heart disease Unclear Respiratory infection Suspicion of SIDS Suspicion of SIDS Unclear Suspicion of SIDS Suspicion of child abuse Suspicion of SIDS Respiratory infection Head injury Intestinal volvulus Unclear Foreign body aspiration Drowning Head injury Unclear Unclear
SIDS SIDS Disease Unclear Unclear SIDS Unclear Unclear SIDS Disease Unclear Disease SIDS SIDS Unclear SIDS Abuse SIDS Disease Accident Disease Unclear Accident Accident Accident Unclear Unclear
4048 4092 3520 5000 4226 5136 6100 6300 5600 6400 5490 7000 7400 4900 6500 9900 4802 9300 9600 12,100 9900 10,200 15,400 13,700 15,000 18,000 22,500
54.5 57.0 52.0 54.0 58.0 62.0 56.0 63.0 60.0 64.0 60.0 70.0 66.0 70.0 61.0 71.0 66.0 78.0 78.0 82.0 79.0 75.0 82.0 87.0 83.0 108.0 119.0
11.2 9.0 18.8 14.9 13.9 35.6 15.1 20.5 30.4 23.6 20.0 10.9 24.9 54.6 46.7 18.8 5.3 40.7 25.6 17.6 22.6 17.8 24.0 27.8 18.8 17.8 36.0
76.3 66.4 59.7 59.2 52.8 71.1 53.1 61.9 60.9 68.5 65.1 57.2 71.5 56.9 59.9 70.4 60.8 61.3 69.5 78.8 68.1 73.7 72.7 67.4 72.2 73.7 64.7
13 17 25 21 18 43 18 25 40 29 25 18 34 68 48 31 7 55 35 30 23 24 25 36 17 29 54
Abbreviation: SIDS, sudden infant death syndrome.
the volume and mean CT attenuation values were obtained using the ‘‘compute volume’’ command. Each subject’s age in days, height (cm), body weight (g), thymic weight (g) and cause of death were obtained from the autopsy records. This study was performed in accordance with the laws of the city of the Hamburg and the data production and ethical guidelines of the University Medical Center Hamburg-Eppendorf. The authors have no conflict of interest directly relevant to the content of this article. 3. Results
Fig. 1. Horizontal sections of the thymus on CT images taken at the level of the carina. The green line indicates the thymic border and a region of interest. (a) A 10month-old female with thymic involution (Case No. 17 in Table 1). (b) A 12-monthold male without thymic involution (Case No. 18).
The thymic volume and CT attenuation values in all cases examined are summarized in Table 1. The relation between thymic weight and volume was investigated using Pearson’s correlation coefficient test. A statistically significant (p < 0.001) strong correlation (r = 0.95) was observed between thymic weight and volume (Fig. 2). Case No. 17, who was suspected to be a victim of child abuse, presented obvious thymic involution, e.g., thinning of the thickness in a horizontal section on the CT image (Fig. 1a). On the other hand, case No. 18, in which the cause of death seemed to be sudden infant death syndrome (SIDS), did not show thymic involution. A non-involuted thymus shows its thickest slice thickness on the horizontal section at the level of the carina. The involuted thymus in case No. 17 shows thinning but exhibits a roughly rectangular structure on the horizontal section, as in the non-involuted thymus in case No. 18. Fig. 3 shows three-dimensional (3D) images of the thymuses of cases No. 17 (a–c) and No. 18 (d–f). These figures visualize the thickness of the thymus well. The CT attenuation value did not correlate with body height, body weight, thymic volume, thymic weight, or postmortem period.
S. Abe et al. / Legal Medicine 17 (2015) 251–254
Fig. 2. Correlation between thymic weight and volume. r = 0.95, p < 0.001. Weight (g) = 3.072 + 1.164 Volume (cm3). The relation was investigated using Pearson’s correlation coefficient test. The black arrow identifies Case No. 17 with thymic involution.
4. Discussion Thymic volume and weight were well correlated, as shown in Fig. 2. Therefore, thymic weight can be calculated from thymic volume estimates obtained from CT images. The thymic weight calculated from the thymic volume could be compared with the normal thymic weight or with past autopsy reports of cases with thymic involution. The case in which child abuse was suspected showed thymic involution (Figs. 1 and 3), as was also shown in a previous report [2]. A 3D reconstruction of the thymus clearly demonstrates thymic involution (Fig. 3a–c). Although the frontal view of the involuted thymus shows no difference in shape on the 3D images, the thickness was markedly decreased. These 3D images were readily obtainable from CT images by rendering, allowing the thymic involution to be visualized clearly.
253
The thickness of the thymus is a good, single-glance indicator of thymic involution. The thickest slice is generally obtained at the level of the carina on horizontal sections, and thus this slice level is adequate as an initial step in a screening test. The thymic volume and CT attenuation value are not correlated with the postmortem period. Those images that were scanned more than five days after death were excluded from the analysis since the thymic borders were difficult to detect. Extremely lowresolution images were not suitable for this analysis. The scan condition should be examined for children with small bodies in order to detect the thymic border correctly. Furthermore, mediastinum lesions such as hemorrhages caused by cardiac compression might obscure the thymic border on CT images. Mediastinum lesions are always considered in order to obtain an accurate assessment of the border. We considered a 10-mm slice thickness to be the minimum requirement in this method. Breiman et al. compared the spleen volume measured on CT images to that measured after surgical resection, and they reported that the mean percentage error in detecting the spleen volume using the sum-of-areas technique was 3.59% at a 10-mm scan spacing [5] This error rate is considered to be adequate. No differences in volume were observed between those calculated using scans semi-automatically set at 10-mm intervals and those manually set at different intervals (<10 mm) on all slice sections. Thymic volume evaluation was applicable only in prepubescent cases because of the pubertal onset of age-related physiological thymic involution. The adult thymus with age-related involution shows a triangular structure on CT images [6,7]. An involuted thymus in childhood, however, maintains a rectangular structure; i.e., it differs significantly in shape from age-related physiological involution. The thymus is morphologically fixed by connective tissues in the mediastinum; when rapid involution of the thymus occurs due to stress, the shape of the thymus maintains its rectangular structure in CT images. The key advantage of evaluating thymic volume by CT scan is to be able to demonstrate thymic involution less invasively in a surviving victim. The evaluation of thymic volume may help pediatricians, psychiatrists, and other health professionals in hospitals to recognize child maltreatment and allow them to intervene at an early stage.
Fig. 3. The 3D images of the thymus obtained from CT images by rendering. (a–c) Case No. 17 with thymic involution. (d–f) Case No. 18 without thymic involution. The 3D images visualize the thickness of the thymus well.
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S. Abe et al. / Legal Medicine 17 (2015) 251–254
The detection of child maltreatment without obvious findings, such as injuries, growth retardation, mental problems, etc., is very difficult. Thymic volume evaluation may provide an opportunity to recognize cases of psychological abuse and/or neglect without specific findings at an early stage. Thus, we believe that the volume of the thymus should be evaluated as routinely as possible in neonates, infants, and children in cases in which child maltreatment is suspected. Ultrasonography is a common diagnostic imaging method and should be the first-choice examination for living victims because it is much less invasive than other methods. It should be noted that performing thymic ultrasonography requires a certain level of proficiency. In the future, 3D ultrasonography may be efficacious for thymic volume evaluation. Prodhomme et al. reported that the virtual volume obtained using magnetic resonance imaging (MRI) was scarcely different from the real volume measured by the water replacement method at autopsy [8]. MRI is a promising imaging method, but it is not yet generally available in forensic medicine. Stress-induced thymic involution will not only occur in cases of child maltreatment; it can also be caused by bacterial infection [9], viral infection (especially HIV [10]), ionizing radiation [11], restraint, starvation [12], or chemotherapy [13]. Meanwhile, myasthenia gravis and hyperthyroidism may induce thymic hyperplasia [14,15]. These anamneses and thymus neoplasms should be investigated carefully to assess the causes of thymic volume abnormalities. Physiological thymic involution seldom occurs in early childhood; the screening test for thymic involution must be exploited for disclosing child maltreatment. In conclusion, we revealed that thymic volume and weight were well correlated. CT is valuable for detecting the presence of stressful environments in childhood. Further investigation is needed to reveal what specific stressful environments could be related to thymic findings. Clinical CT images could be used to investigate thymic volume changes in surviving victims. The comparison of postmortem microscopic investigations with CT findings should be performed to reveal the correlations between histological structure and CT findings with regard to the thymus, particularly in terms of the CT attenuation value. Additional research should improve the accuracy and usability of this method.
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