Autopsy Weights Research Articles

Noninvasive estimation of heart organ mass by postmortem magnetic resonance imaging and computed tomography compared to conventional autopsy in fetuses: a pilot study

ObjectivesThe purpose of this pilot study is to investigate the accuracy of mass estimation of the heart using postmortem MRI and CT in this population. MethodsThe mass of the heart was estimated using three different methods: sequential segmentation of the right and left ventricles by MRI in 30 patients; sequential segmentation of the left ventricle chamber using CT and an ellipsoid method of the left ventricle (LV) using CT in 6 patients. The estimated mass by each method was compared to conventional autopsy mass using linear regression. ResultsThe correlation between estimated and measured cardiac mass using postmortem MRI measurements of the right and left ventricles, CT derived volumes of the left ventricle, or by the LV ellipsoid CT method are as follows: y = 0.87744x - 0.74813 (R2 = 0.958); y = 0.6004x - 2.16 (R2 = 0.8681); y = 0.6019 - 2.1615 (R2 = 0.8599), respectively. When separating the fetuses evaluated by pmMRI into a ≤20 weeks subset or >20 weeks subset, the correlation are as follows: y = 0.5176x + 0.2428 (R2 = 0.645) and y = 0.91237x - 1.53647 (R2 = 0.9475), respectively. ConclusionMass of the heart at autopsy modestly correlates with MRI derived volumes measuring the right and left ventricles. The small sample in the CT derived volume of the left ventricle alone or by the simplified estimated method using the ellipsoid measurements of the left ventricle by CT compared to autopsy weights make it difficult to conclude CT's utility using these methods.

Autopsy-Based Growth Charts May under-Detect Fetal Growth Restriction at Autopsy

Background: Accurate identification of fetal growth restriction in fetal autopsy is critical for assessing causes of death. We examined the impact of using a chart derived from ultrasound measurements of healthy fetuses (World Health Organization fetal growth chart) versus a chart commonly used by pathologists (Archie et al.) derived from fetal autopsy-based populations in diagnosing small-for-gestational-age (SGA) birth in perinatal deaths. Study Design: We examined perinatal deaths that underwent autopsy at BC Women’s Hospital, 2015-2021. Weight centiles were assigned using the ultrasound-based fetal growth chart for birthweight and autopsy-based growth chart for autopsy weight. Results: Among 352 fetuses, 30% were SGA based on the ultrasound-based fetal growth chart versus 17% using the autopsy-based growth chart (p < 0.001). Weight centiles were lower when using the ultrasound-based versus autopsy-based growth chart (median difference of 9 centiles [IQR 2, 20]). Conclusions: Autopsy-based growth charts may under-classify SGA status compared to ultrasound-based fetal growth charts.

Improving the quality of preclinical research echocardiography: observations, training, and guidelines for measurement.

Informal training in preclinical research may be a contributor to the poor reproducibility of preclinical cardiology research and low rates of translation into clinical research and practice. Mouse echocardiography is a widely used technique to assess cardiac structure and function in drug intervention studies using disease models. The interobserver variability of clinical echocardiographic measurements has been shown to improve with formalized training, but preclinical echocardiography lacks similarly critical standardization of training. The aims of this investigation were to assess the interobserver variability of echocardiographic measurements from studies in mice and address any technical impediments to reproducibility by implementing standardized guidelines through formalized training. In this prospective, single-site, observational cohort study, 13 scientists performing preclinical echocardiographic image analysis were assessed for measurement of short-axis M-mode-derived dimensions and calculated left ventricular (LV) mass. Ten M-mode images of mouse hearts acquired and analyzed by an expert researcher with a spectrum of LV mass were selected for assessment and validated by autopsy weight. After the initial observation, a structured formal training program was introduced, and accuracy and reproducibility were reevaluated. Mean absolute percentage error for expert-calculated LV mass was 6 ± 4% compared with autopsy LV mass and 25 ± 21% for participants before training. Standardized formal training improved participant mean absolute percentage error by ~30% relative to expert-calculated LV mass ( P < 0.001). Participants initially categorized with high-range error (25-45%) improved to low-moderate error ranges (<15-25%). This report reveals an example of technical skill training insufficiency likely endemic to preclinical research and provides validated guidelines for echocardiographic measurement for adaptation to formalized in-training programs. NEW & NOTEWORTHY The informal training common to academic/research institutions may be a contributor to the relatively poor reproducibility observed for preclinical cardiac research. In our observation of echocardiography analysis in murine models, we present evidence of moderate interobserver variability in standard preclinical research practice at an Australian heart research institute. These observations give rise to our recommendations for practical guidelines for echocardiography analysis in an adaptable approach to general preclinical research skill training. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/preclinical-echocardiography-training-and-guidelines/ .

Comparison of the cardiothoracic ratio between postmortem and antemortem computed tomography.

As postmortem imaging has gained prominence as a supplement to traditional autopsy, it is important to understand the normal postmortem changes to enable the accurate evaluation of postmortem imaging. No studies have evaluated the postmortem changes in cardiothoracic ratio (CTR) compared with antemortem images in the same subjects. We studied 147 consecutive subjects who underwent antemortem and postmortem CT, and autopsy. Postmortem CT was performed <23h after death and was followed by autopsy. The subjects were divided into three groups: normal heart, old myocardial infarction, and CPR-treated hearts. CTR was compared between antemortem and postmortem CT using paired t tests, which revealed that the CTR was greater on postmortem CT than on antemortem CT in all groups (mean CTR: 0.53±0.06vs. 0.50±0.06, respectively; P<0.01). Sex, age, time elapsed since death, and the causes of death were examined as potential confounding factors for the postmortem changes in CTR, but no significant associations were found. Receiver-operating characteristic (ROC) curves were used to determine CTR values for cardiomegaly, which was defined according to the autopsy weight of the heart. The area under the ROC curve was 0.71 (95% confidence interval 0.63-0.79). The CTR threshold of 0.54 identified cardiomegaly with the greatest accuracy, compared with the general threshold of 0.50. In conclusion, the CT-determined CTR increases after death, irrespective of the heart's condition. We should be cautious of overdiagnosis of cardiomegaly on postmortem CT, and new criteria for interpreting cardiomegaly on postmortem CTR are needed.

Effects of intrauterine retention and postmortem interval on body weight following intrauterine death: implications for assessment of fetal growth restriction at autopsy.

According to the classification system used, 15-60% of stillbirths remain unexplained, despite undergoing recommended autopsy examination, with variable attribution of fetal growth restriction (FGR) as a cause of death. Distinguishing small-for-gestational age (SGA) from pathological FGR is a challenge at postmortem examination. This study uses data from a large, well-characterized series of intrauterine death autopsies to investigate the effects of secondary changes such as fetal maceration, intrauterine retention and postmortem interval on body weight. Autopsy findings from intrauterine death investigations (2005-2013 inclusive, from Great Ormond Street Hospital and St George's Hospital, London) were collated into a research database. Growth charts published by the World Health Organization were used to determine normal expected weight centiles for fetuses born ≥ 24 weeks' gestation, and the effects of intrauterine retention (maceration) and postmortem interval were calculated. There were 1064 intrauterine deaths, including 533 stillbirths ≥ 24 weeks' gestation with a recorded birth weight. Of these, 192 (36%) had an unadjusted birth weight below the 10th centile and were defined as SGA. The majority (86%) of stillborn SGA fetuses demonstrated some degree of maceration, indicating a significant period of intrauterine retention after death. A significantly greater proportion of macerated fetuses were present in the SGA population compared with the non-SGA population (P = 0.01). There was a significant relationship between increasing intrauterine retention interval and both more severe maceration and reduction in birth weight (P < 0.0001 for both), with an average artifactual reduction in birth weight of around -0.8 SD of expected weight. There was an average 12% reduction in fetal weight between delivery and autopsy and, as postmortem interval increased, fetal weight loss increased (P = 0.0001). Based on birth weight alone, 36% of stillbirths are classified as SGA. However, fetuses lose weight in utero with increasing intrauterine retention and continue to lose weight between delivery and autopsy, resulting in erroneous overestimation of FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Abstract 17984: Validating the Gold-standard: Steady-State Free Precession Sequence for Assessment of Left Ventricular and Right Ventricular Mass

Background: Left ventricular (LV) mass (LVM) predicts cardiovascular morbidity and mortality, thus accurate quantification of LVM is essential. Cardiac magnetic resonance (CMR) is considered the gold-standard for LVM and right ventricular (RV) mass (RVM) quantification. The steady-state free precession (SSFP) is the most widely used sequence nowadays; however, SSFP-derived LVM/RVM has only been validated in normal animals, while CMR is usually performed under pathological conditions. Therefore, our objective was to validate in vivo SSFP-derived LVM/RVM with the gold-standard autopsy weights of experimental animals with myocardial infarction (MI), LV remodeling, and pulmonary hypertension (PH). Methods: MI was induced in 11 pigs by balloon occlusion of the proximal LAD for 60 min, and MRIs were obtained 2 months post-MI. PH was induced in 11 pigs by surgical ligation of three pulmonary veins and animals underwent CMR 4 months post-surgery. Animals were euthanized immediately after CMR. Each ventricle was separately weighted using a high-fidelity scale. MRI studies were performed with a 3.0 Tesla magnet. Results: In the MI model, infarct size (IS) was 29±6% of LV, LVEF 34±8%, RVEF 62±149%, mean pulmonary artery pressure (mPAP) 16±4mmHg, and pulmonary vascular resistance (PVR) 2.3±1.1 Wood units. In the PH model, IS was 0%, LVEF 64±5%, RVEF 55±10%, mPAP 36±16mmHg and PVR was 7.2±5.5 Wood units. All animals provided images of diagnostic quality. Excellent correlations were obtained between SSFP-calculated LV mass (86.6±12.9g) and autopsy-measured LV mass (91.1±15.2g, r=0.97, p&lt;0.001). For LV, the correlation was not different in both groups of animals (r=0.98, p=0.01 for post-MI animals; r=0.96, p=0.01 for PH animals). There was also a strong correlation between RV mass obtained from CMR (37.9±14.1g) and from autopsy (41.6±13.1g r=0.9, p=0.01). For RV, the correlation was higher in PH animals (r=0.92, p&lt;0.001) than in post-MI pigs (r=0.8, p=0.01). Conclusions: In vivo SSFP-CMR sequences determine LVM and RVM accurately and reliably compared with autopsy. Therefore, our study provides further validation for the clinical use of SSFP sequence derived LVM and RVM.

Fetal organ weight estimation by postmortem high‐field magnetic resonance imaging before 20 weeks' gestation

To ascertain whether high-field magnetic resonance imaging (MRI) allows accurate estimation of the weight of various fetal organs at postmortem before 20 weeks' gestation. From 23 fetuses at 9-20 weeks, following termination of pregnancy or in-utero fetal death (IUFD), 207 assorted fetal organs were evaluated by high-field MRI at 9.4 T prior to conventional autopsy. Fetal organ density was calculated by correlating volume and weight at autopsy using linear regression analysis, and this was used to estimate fetal organ weight by MRI. The relative error in MRI estimation of organ weight was calculated as follows: (|MRI weight - autopsy weight|/autopsy weight) × 100 (%). Multiple regression analysis was used to investigate the effect on the relative error of MRI organ weight estimates of gestational age at TOP or delivery following IUFD, autopsy weight, fetal organ examined, IUFD and fetal maceration. Of the 207 organs evaluated, 133 (64%) were examined for fetal organ density and 155 (75%) for fetal organ weight. Fifty-two organs were excluded from our analysis; 41 of these were from fetuses with IUFD, with 39 organs macerated. In 32 cases, exclusion was due to an inability to assess the organ both on MRI and on conventional autopsy. Volume and weight at autopsy correlated significantly, following the linear equation: autopsy volume = (0.9947 × autopsy weight) - 4.7556, where autopsy volume is in mm(3) and weight is in mg (r = 0.99, P < 0.001). Overall the mean relative error in the MRI estimation of organ weight was 68%. Multiple regression analysis showed that the relative error in the MRI estimation of organ weight was significantly associated with gestational age at TOP or delivery following IUFD and fetal maceration, but not with autopsy weight, fetal organ examined or IUFD. In the subgroup of non-macerated organs and for fetuses above 14 weeks' gestation, the mean relative error in the MRI estimation of organ weight was 34%. In fetuses before 20 weeks' gestation, noninvasive estimation of organ weight is feasible using high-field MRI, but there is a mean overestimation. Limitations of the technique occur mainly in cases of small macerated fetuses before 14 weeks' gestation.

ADRENAL WEIGHT AND SERUM CHOLESTEROL CONCENTRATION IN RABBITS WITH DIFFERENTIAL CHOLESTEROLAEMIC RESPONSE TO CHOLESTEROL FEEDING.

The question addressed is whether in rabbits a relationship exists between serum cholesterol response to dietary cholesterol and adrenals autopsy weight. For this purpose we have measured adrenals weight and serum cholesterol levels in backcross and F2-intercross progeny of a cross between IIIVO/JU (dietary cholesterol resistant) and AX/JU (dietary cholesterol susceptible) rabbits. The animals were fed a commercial, pelleted diet enriched with 0.3% (w/w) cholesterol during a test period which lasted 41 (backcross rabbits) or 78 (F2-intercross rabbits) days. After the test period hyperresponders with high serum cholesterol levels and hyporesponders with low serum cholesterol levels could be distinguished from normoresponders, both within backcross and F2-intercross rabbits. A positive relationship between serum cholesterol response and adrenals weight was found for male, but not for female F2-intercross rabbits. No clear dose-response relationship between serum cholesterol response and adrenals weight was found both for male and female backcross rabbits. It is concluded that the relationship between serum cholesterol response and adrenals weight in rabbits is certainly not a simple one and may depend on gender, duration of the experimental period and the genetic background of the animals.

Increased liver weights in severely burned children: comparison of ultrasound and autopsy measurements

Hepatomegaly is a common finding at autopsy in severely burned children surviving less than 6 months. This study validates a reliable ultrasound method which can be used to identify changes in liver size in severely burned children during acute hospitalization. Thirty-eight children, age 0.5–17 years with burns covering over 40% of their total surface area were studied at autopsy. Liver weight was measured at autopsy and compared to predicted liver weight for age and height. Eighteen had liver size measured by ultrasound within 10 days of death while five had ultrasound liver measures after death just prior to autopsy. All burned children who survived 7 days or more ( n=33) had liver weights at autopsy that were greater than predicted for age and height while all 23 livers measured by ultrasound were greater than predicted. Autopsy weights correlated well with weights estimated by ultrasound, R=0.824. At autopsy, those who survived 7 days or more had enlarged livers ranging from 142 to 406% of their predicted normal age and height. Common histologic findings include large and small-droplet fat deposits, and cholestasis. The degree of these histologic abnormalities correlated with the increase in liver weight, R=0.652. Ultrasound is a valid, noninvasive method for measuring liver weight changes in severely burned children during acute hospitalization. Ninety-five percent of the severely burned children from this institute had significant hepatomegaly identified at autopsy.

Long Term Infusion of Subpressor Doses of Angiotensin II Causes a Delayed Vasoconstriction in the Fetal Placental Circulation of the Sheep † 949

The kidney plays a pivotal role in long term regulation of arterial blood pressure (BP) in the postnatal mammal. Fetal BP may also be controlled by the kidney through a mechanism that alters the rate of net transplacental water acquisition. Prolonged angiotensin (Ang) infusion at a rate that does not change in BP in the short term, causes a slow but substantial rise in BP in both intact and nephrectomized fetal lambs. Angiotensin infusion at the same rate also increases water transfer from mother to conceptus, resulting in polyhydramnios or hydrops fetalis. The present studies were conducted to test the hypothesis that a crucial regulatory role for Ang II in the process of transplacental water acquisition is to cause precapillary vasoconstriction of the placental circulation. This would decrease fetal placental blood flow and the hydrostatic pressure in the fetal placental capillaries, thereby promoting filtration of water towards the fetus. Two intact and 4 bilaterally nephrectomized fetuses at 117-125 d of gestation were instrumented with flow sensor (Transonics), and arterial and venous cathethers. After 2 days of recovery, 5 days of control measurements demonstrated stable BP and umbilical flow. A continuous fetal infusion of Ang II (132 ± μg/d per kg autopsy weight, mean ± SD) was given for 5 days. Ang II rose from 17± 3 pg/ml to 244 ± 51 pg/ml, and did not change over the 5 days. Control BP was 41.5 ± 5 mm Hg. One h after start of infusion BP was 44.5 ± 5 mm Hg, a nonsignificant change. BP then rose at a rate of 3.8 mm Hg per day. One h after stopping Ang II infusion, BP fell by 17.6 ± 3.8 mm Hg, but it remained 8.3 ± 3.0 mm Hg above control, p<0.025. Also, 1 h after starting Ang II infusion, umbilical flow was not significantly decreased. There was no later change in mean flow despite the large increase in BP. After 1 hr of infusion, fetal placental resistance was only 9% greater than control, NS; but after 5 days of Ang II infusion, resistance had almost tripled. This increased resistance was not dependent on circulating Ang II; 1 h after infusion, 69% of the increase in resistance remained. Ang II, continuously infused at a rate that causes a negligible immediate increase in fetal BP and resistance, results in a very slow, but very large increase in fetal placental resistance that is not due to a direct action of circulating Ang II. This result is compatible with a structural alteration of the umbilical vascular bed with long term exposure to a high physiological concentration of Ang II.

Comparison of electron beam computed tomography scanning and magnetic resonance imaging quantification of right ventricular mass: Validation with autopsy weights

We compared, in the same human hearts, the ability of magnetic resonance (MR) imaging and electron beam computed tomography (CT) scanning to accurately quantify the free wall and septal components of right ventricular (RV) mass. Eleven hearts extracted at autopsy were subjected to MR imaging and electron beam CT scanning in short-axis projections. Regression analyses of mass determinations obtained by manual planimetry MR imaging and electron beam CT scanning and autopsy weights were performed. RV free wall mass by both MR imaging (53.4 +/- 19.1 g) and electron beam CT scanning (53.9 +/- 20.4 g) correlated well with autopsy weight (57.7 +/- 20.2 g). Regression analysis showed a strong correlation for MR imaging (r = .88, slope = .88, standard error the estimate [SEE] = 7.2 g, p < .001) and electron beam CT scanning (r = .95, slope = .95, SEE = 6.6 g, p < .001). RV septal mass by MR imaging (10.8 +/- 3.5 g) and electron beam CT scanning (7.1 +/- 2.4 g) correlated less well with the autopsy weight (12.5 +/- 6.5 g). Regression analysis showed a fair correlation for MR imaging (r = .45, slope = .83, SEE = 2.05 g, p = .001) and a poor correlation for electron beam CT scanning (r = .46, slope = .17, SEE = 2.25 g, p = .57). Both MR imaging and electron beam CT scanning accurately predict RV free wall mass but have difficulty predicting the septal component. Because the septal component constitutes only a small proportion of the total RV mass, determinations of RV mass should be based solely on the free wall component.

Right ventricular mass measurement by electron beam computed tomography. Validation with autopsy data.

Validation of right ventricular mass quantitation by electron beam computed tomography in humans has not been performed. The ability of electron beam computed tomography to accurately determine the septal component of the right ventricle also has not been determined. This article addresses both issues. Twenty human adult hearts obtained at autopsy were scanned by electron beam computed tomography in a short-axis projection. Planimetry of the right ventricular free wall and septal components of each slice was performed and summed to determine right ventricular mass. These measurements were compared against comparable measurements obtained by autopsy weights of the hearts. Right ventricular free wall weights by electron beam computed tomography (53.9 +/- 18.4 g) correlated well (slope = .92, r = .92, standard error of the estimate = 7.4 g, P < .001) with autopsy weights (55.8 +/- 18.4 g). Right ventricular septal weights by electron beam computed tomography (6.1 +/- 2.3 g) correlated poorly (slope = .04, r = .11, standard error of the estimate = 2.4 g, P = .65) with autopsy weights (13.9 +/- 6.3 g). Electron beam computed tomography quantitation of right ventricular mass is accurate in humans if only the free wall and not the septal component is utilized.

Accuracy and reproducibility of clinically acquired two-dimensional echocardiographic mass measurements

Left ventricular mass (LVM) measurements made by the truncated ellipsoid algorithm from clinical two-dimensional echocardiograms (2DE) were compared to autopsy weights in 37 patients. All six 2DE instruments were calibrated with an ultrasound phantom to standardize LVM measurements. Measurements were made by an experienced echocardiographer (LVM E) and by an echocardiographer (LVM N) newly trained in LVM measurement from clinical 2DE tapes of patients with LV weights later confirmed at autopsy. LVM E ( r = 0.91, SEE ± 41 gm) were more accurate than LVM N for all 2DE, but LVM N equalled LVM E in accuracy for technically good 2DE. Interobserver variability was 36 gm, or 17% of LVM for all 2DE, and fell to 27 gm, or 12% of LVM for technically good 2DE. Segmental wall motion abnormalities and time from 2DE to death did not influence measurement accuracy significantly. LVM measurements by the 2DE truncated ellipsoid formula are accurate and reproducible in patients with normal and abnormal hearts.

A Ten-Year Retrospective Study of Pink and Yellow Neonatal Hyaline Membrane Disease

Since it was first described several years ago, yellow bilirubin staining of the pulmonary membranes in neonatal hyaline membrane disease has apparently become more common. In a retrospective study of neonatal autopsy experience, it was found that as more of the premature infants survived longer, yellow hyaline membrane disease was a more frequent finding, increasing from 7% of all newborns having hyaline membrane disease at autopsy in 1970 to 50% in 1980. In comparing 499 cases with eosinophilic hyaline membranes with 168 cases of yellow membranes, newborns with bilirubin staining of the pulmonary membranes were found to be more premature (P less than .02), had smaller autopsy weight (P less than .002), and survived longer (P less than .00001). When multiple clinical parameters were compared between a group of infants with yellow membranes and a group of infants with pink membranes who were matched for gestational age, year of birth, and length of survival, no differences were found between the two groups. No correlation was found between kernicterus and yellow staining of the pulmonary hyaline membranes in the first years of the study, but there was a strong correlation in the last 5 years, coincident with the increase in the rate of yellow hyaline membrane disease found at autopsy. The gross bilirubin staining of the brain was the secondary type of kernicterus, not toxic bilirubin encephalopathy. The observation of bilirubin staining in the lung and in the brain correlates with prolonged survival in some very small premature infants. This does not appear to be a manifestation of bilirubin toxicity, but rather a marker of prior tissue damage.

Tannic acid-induced alterations in mouse growth and pituitary melanocyte-stimulating hormone activity

Male albino mice were fed a diet containing 5 or 8% ( w w ) tannic acid in ground laboratory chow. Initial weights of mice ranged from 7 to 18 g and the duration of feeding from 3 to 8 wk. Body weights were taken at weekly intervals for all animals. At autopsy weights were taken of the testes, adrenals and pituitary glands and the latter were reserved for subsequent frog skin bioassay of melanocyte-stimulating hormone (MSH). The two test groups with initial body weights of 17.5–18.3 g demonstrated depressed growth initially, but had reached the body weight of untreated mice at time of autopsy. These groups showed no meaningful difference in testes, adrenal or pituitary weights or in pituitary MSH activity. Animals with the lowest initial weights (7–11.3 g) had continued depressed growth until the time of autopsy and exhibited a significant increase in pituitary MSH activity. It appears that young mice may be more susceptible to the effects of feeding tannic acid. The increase in pituitary MSH activity may be considered as evidence of the toxic effect of prolonged feeding of tannic acid, possibly occurring at the level of the hypothalamus.

Poverty and Race: Effects on Prenatal Nutrition

Perinatal mortality rates are higher in the U.S. than in many other nations. An excess number of low birth weight infants in families of low socioeconomic status accounts for much of this high perinatal mortality. Necropsy material was examined from 1,002 consecutive autopsies on stillborn and newborn infants. 449 of the cases were excluded because of disorders that might have affected fetal growth. Income data was available on 469 of the remaining cases and they were classified by economic status using a U.S. Government poverty index. Autopsy weights and measurements were calculated in percent of published normal mean values.

Left ventricular mass: A comparison of angiocardiographic measurements with autopsy weight

A previously described angiocardiographic method has been used to determine left ventricular mass in 28 patients. Weight of the left ventricle at autopsy has been compared with calculated mass. The method has been shown to be reliable in the absence of marked right ventricular hypertrophy, pericardial effusion, or adhesive pericarditis.