Standardizing Minimally Invasive Tissue Sampling of Postmortem Brain Using Bard Monopty Needle in Newborns with Neurological Injury

Figures & data

Figure 1. Brain Bard Monopty needle with brain core.

Figure 2. Procedure for collection of brain cores from the anterior and posterior fontanel.

Table 1. Gestational age and head circumference of newborns.

Case no.	Gestational age (weeks)	Head circumference (cm)
1.	22	19
2.	24	22
3.	24	21
4.	24	23
5.	25	25
6.	26	23
7.	26	24.5
8.	28	23.5
9.	29	27
10.	29	24.5
11.	30	28.5
12.	30	30
13.	30	25
14.	30	27
15.	30	24
16.	30	27
17.	34	31
18.	35	31
19.	36	33
20.	37	32.5

Table 2. Histopathological findings of MITS from anterior and posterior fontanel.

CASE no.	Brain tissue-Anterior fontanel					Brain tissue-Posterior fontanel
	Mark 0	Mark 1	Mark 2	Mark 3	Mark 4	Mark 1	Mark 2	Mark 3
Group A – Gestational age − 22–27 weeks, Head circumference 19–25 cm
1.	Periventricular area with germinal matrix	White matter microhemorrhage Cortical tissue	White matter	Periventricular area with germinal matrix White matter	Bone	Periventricular area with germinal matrix microhemorrhage Choroid plexus with hemorrhage Anoxic neurons Reactive glial cells	White matter Anoxic neurons Reactive glial cells	Meningeal hemorrhage Periventricular area with germinal matrix microhemorrhage White matter Anoxic neurons Reactive glial cells
2.	White matter microhemorrhage Periventricular area with GMH, IVH	Hemorrhage	Hemorrhage	Hemorrhage	Bone	Choroid plexus hemorrhage	Meninges Fragment of hemorrhage	Occipital cortex with neurons White matter
3.	WMH GMH	Periventricular area	Periventricular area with germinal matrix	Periventricular area with germinal matrix congestion White matter	Bone	White matter with Anoxic neurons Reactive astrocytes	White matter	White matter microhemorrhage Periventricular area with germinal matrix
4.	Periventricular area with white matter	Dura matter White matter	Periventricular area with germinal matrix congestion	Meninges Periventricular area with WMH	Bone	White matter Congestion	White matter Anoxic neurons	Bone
5.	White matter congestion	White matter Cortical tissue	White matter congestion Periventricular area with germinal matrix microhemorrhage Reactive astrocytes	SAH White matter microhemorrhage Periventricular area with GMH Anoxic neurons	Meninges White matter microhemorrhage	Meninges White matter congestion Periventricular area microhemorrhage Anoxic neurons	White matter congestion	White matter congestion Anoxic neurons
6.	White matter microhemorrhage Reactive astrocytes	White matter	Periventricular area with germinal matrix hemorrhage Reactive astrocytes	White matter microhemorrhage Cortical tissue Reactive astrocytes	Bone	Meninges Subarachnoid hemorrhage WMH Periventricular area	White matter microhemorrhage GMH	Subarachnoid hemorrhage White matter microhemorrhage Periventricular area Cortical tissue Anoxic neurons
7.	Subdural hemorrhage White matter Cortical tissue	White matter Periventricular area with germinal matrix Microhemorrhage	White matter microhemorrhage	White matter	Dura matter	Meninges White matter microhemorrhage Anoxic neurons Reactive astrocytes	Meninges with SAH White matter Anoxic neurons Reactive astrocytes	White matter microhemorrhage Anoxic neurons Reactive astrocytes
Group B -Gestational age − 28–37 weeks, Head circumference 23 − 33 cm
8.	Dura matter Cortical tissue	Meninges Cortical tissue WMH	Periventricular area with GMH Intraparenchymal hemorrhage	GMH	Meninges SAH	Fragment of Hemorrhage	White matter microhemorrhage Anoxic neurons Reactive astrocytes	Fragment of hemorrhage White matter Anoxic neurons
9.	Dura matter Cortical tissue	Meninges White matter	Meninges White matter with microhemorrhage	White matter Periventricular area with GMH Choroid plexus with congestion	White matter Anoxic neurons Reactive astrocytes Glial nodules	Cerebellum	White matter Cortical tissue	Fibrous tissue
10.	White matter congestion Microhemorrhage Reactive astrocytes	White matter congestion Reactive astrocytes	White matter microhemorrhage Periventricular area with germinal matrix congestion	White matter with congestion Periventricular area with germinal matrix with congestion	White matter	Choroid plexus hemorrhage Cerebellum Periventricular area Reactive astrocytes	White matter with anoxic neurons	Cartilage
11.	Meningeal congestion	White matter congestion	Large blood vessel	White matter congestion Reactive astrocytes	Cortical tissue and White matter microhemorrhage	Meninges Periventricular area with germinal matrix congestion Occipital cortex with reactive astrocytes	WMH Occipital cortex Anoxic neurons	White matter Anoxic neurons
12.	Meninges SAH Dura matter White matter	White matter microhemorrhage	White matter microhemorrhage	Meningeal layer with focus of neutrophils WMH	White matter Anoxic neurons Reactive astrocytes	Anoxic neurons	White matter Anoxic neurons Reactive astrocytes	White matter microhemorrhage
13.	Meninges Dura matter hemorrhage Cortical tissue congestion	White matter congestion White matter microhemorrhage Cortical tissue	White matter Congestion	White matter Periventricular area with germinal matrix congestion Reactive astrocytes	White matter with Reactive astrocytes Cortical tissue congestion	Fibrous tissue	White matter Congestion Cortical tissue congestion Reactive astrocytes	Cortical tissue
14.	White matter	White matter	White matter Periventricular area with germinal matrix	White matter Reactive astrocytes	White matter	White matter microhemorrhage Anoxic neurons Reactive astrocytes	White matter microhemorrhage Reactive astrocytes	Occipital cortex Anoxic neurons
15.	White matter microhemorrhage Cortical tissue hemorrhage Anoxic neurons Reactive astrocytes	Dura matter White matter Cortical tissue Periventricular area with germinal matrix congestion Reactive astrocytes	White matter Periventricular area with germinal matrix congestion Microhemorrhage GMH Reactive astrocytes	White matter Reactive astrocytes	White matter Cortical tissue Anoxic neurons	Meninges SAH Choroid plexus Cerebellum	Congested meninges Occipital cortex	White matter microhemorrhage Anoxic neurons
16.	Dura matter White matter congestion Cortical tissue	White matter congestion Intraparenchymal hemorrhage Anoxic neurons	Periventricular area with germinal matrix Reactive astrocytes	White matter Periventricular area with germinal matrix and congestion Anoxic neurons	White matter microhemorrhage Cortical tissue	Occipital cortex congestion Periventricular area Anoxic neurons	White matter congestion Cerebellum Anoxic neurons	White matter Cortical tissue Anoxic neurons
17.	White matter Congestion	SAH White matter	White matter microhemorrhage and congestion	White matter microhemorrhage and congestion	White matter microhemorrhage Cortical tissue Large fragments of hemorrhage	SAH Small fragments of hemorrhage	SAH	Fragments of hemorrhage
18.	Dura matter	Cortical tissue microhemorrhage	Meninges Subarachnoid area Periventricular area with white matter Parenchyma shows fungal hyphae	White matter Periventricular area Germinal matrix	White matter Periventricular area	Fibrous tissue	Meninges White matter Periventricular area Reactive astrocytes	Anoxic neurons
19.	Dura matter White matter	Meninges Subarachnoid congestion with congested vessels White matter Cortical tissue	White matter congestion Cortical tissue SAH	Periventricular Focal Germinal matrix Ependymal rosettes	White matter Cortical tissue Anoxic neurons	White matter Cortical tissue	Fibrous tissue	Periventricular area Cerebellum Choroid plexus congestion
20.	White matter microhemorrhage Cortical tissue	White matter microhemorrhage	White matter	White matter microhemorrhage Periventricular area	Meninges Dura matter microhemorrhage Congested subarachnoid layer Cortical tissue White matter Anoxic neurons Reactive astrocytes	Dura matter	Meninges SAH White matter	Occipital cortex White matter Reactive astrocytes Anoxic neurons

HI: Hypoxic ischemia; SAH: Subarachnoid Hemorrhage; GMH: Germinal matrix hemorrhage; IVH: Intraventricular Hemorrhage; WMH: White matter hemorrhage.

Figure 3. Histopathological findings (a) Subarachnoid hemorrhage, (b) Parenchymal microhemorrhage with anoxic neurons, (c) Periventricular area with germinal matrix with congestion, (d) Meningitis, (e) Cerebellum and (f) Choroid plexus hemorrhage.

Table 3. Findings of MITS and CDA.

Case no.	MITS Findings	CDA Findings
1.	Hypoxic ischemic changes Subarachnoid hemorrhage Germinal matrix microhemorrhage White matter microhemorrhage Choroid plexus hemorrhage	Subarachnoid hemorrhage Periventricular congestion and microhemorrhage Cerebellar hemorrhage
2.	Intraventricular hemorrhage Germinal matrix hemorrhage White matter microhemorrhage Choroid plexus hemorrhage	Meningeal congestion Intraventricular hemorrhage Cerebellar hemorrhage
3.	Hypoxic ischemic changes White matter hemorrhage Germinal matrix hemorrhage	Meningeal congestion Periventricular hemorrhage Choroid plexus congestion
4.	Hypoxic ischemic changes Germinal matrix congestion White matter hemorrhage	Subarachnoid hemorrhage Germinal matrix hemorrhage Periventricular hemorrhage
5.	Hypoxic ischemic changes White matter microhemorrhage Germinal matrix hemorrhage	Intraparenchymal hemorrhage Intraventricular hemorrhage
6.	Hypoxic ischemic changes Subarachnoid hemorrhage White matter hemorrhage Germinal matrix hemorrhage	Meningeal hemorrhage Germinal matrix hemorrhage Intraventricular hemorrhage Intraparenchymal hemorrhage
7.	Hypoxic ischemic changes Subdural hemorrhage Subarachnoid hemorrhage Periventricular area hemorrhage White matter microhemorrhage Germinal matrix microhemorrhage	Meningeal hemorrhage Bilateral periventricular hemorrhage
8.	Hypoxic ischemic changes Subarachnoid hemorrhage White matter hemorrhage Germinal matrix hemorrhage Intraparenchymal hemorrhage	Subarachnoid hemorrhage Intraventricular hemorrhage Intraparenchymal hemorrhage
9.	Hypoxic ischemic changes White matter hemorrhage Periventricular area with germinal matrix hemorrhage Choroid plexus congestion	Meningeal congestion Intraventricular hemorrhage
10.	Hypoxic ischemic changes Periventricular area with germinal matrix congestion White matter congestion Choroid plexus hemorrhage	Meningeal congestion Bilateral germinal matrix congestion Intraventricular hemorrhage
11.	Hypoxic ischemic changes Congested meninges Periventricular area with germinal matrix congestion White matter congestion	Autolytic changes Bilateral germinal matrix congestion
12.	Hypoxic ischemic changes Subarachnoid hemorrhage Meningitis White matter hemorrhage	Hypoxic ischemic changes Meningitis Intraventricular hemorrhage
13.	Hypoxic ischemic changes Dura matter hemorrhage Periventricular area with germinal matrix congestion White matter microhemorrhage and congestion Cortical tissue congestion	Meningeal hemorrhage Intraventricular hemorrhage Intraparenchymal hemorrhage
14.	Hypoxic ischemic changes White matter microhemorrhage	Congested meninges Intraventricular hemorrhage
15.	Hypoxic ischemic changes Subarachnoid hemorrhage Periventricular area with germinal matrix hemorrhage White matter microhemorrhage Cortical tissue hemorrhage	Hypoxic ischemic changes Subarachnoid hemorrhage Periventricular hemorrhage
16.	Hypoxic ischemic changes Intraparenchymal hemorrhage White matter microhemorrhage	Hypoxic ischemia changes Intraparenchymal hemorrhage Cerebellar parenchymal hemorrhage
17.	Subarachnoid hemorrhage Massive hemorrhage White matter microhemorrhage and congestion	Subarachnoid hemorrhage Bilateral germinal matrix congestion Bilateral intraventricular hemorrhage
18.	Hypoxic ischemic changes Cortical tissue microhemorrhage Fungal hyphae in parenchyma	Meningeal congestion Intraventricular hemorrhage Intraparenchymal hemorrhage Choroid plexus hemorrhage Intravascular fungal hyphae and spores
19.	Hypoxic ischemic changes Subarachnoid congestion and hemorrhage Choroid plexus congestion	Subarachnoid hemorrhage Congested blood vessels
20.	Hypoxic ischemic changes Subarachnoid hemorrhage White matter microhemorrhage	Hypoxic ischemic changes Subarachnoid hemorrhage

Table 4. Sensitivity, specificity, PPV, NPV, and associated 95% confidence interval of MITS when compared to CDA.

Parameter	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
Meningeal hemorrhage	62.5 (35.4, 84.8)	75 (19.4, 99.4)	90.9 (58.7, 99.8)	33.3 (7.5, 70.1)
Periventricular hemorrhage	92.3 (64, 99.8)	85.7 (42.1, 99.6)	92.3 (64, 99.8)	85.7 (42.1, 99.6)
Intraventricular hemorrhage	100 (63.1, 100)	91.7 (61.5, 99.8)	88.9 (51.8, 99.7)	100 (71.5, 100)
Parenchymal hemorrhage	83.3 (35.9, 99.6)	100 (76.8, 100)	100 (47.8, 100)	93.3 (68.1, 99.8)

PPV: Positive predictive value; NPV: Negative predictive value.

Data availability statement

The datasets used and analyzed during the current study are attached in the documents. Furthermore, information will be available from the corresponding author upon reasonable request.