Table 2.

Magnetic resonance imaging studies.

First author (Year)	Study population	Sample size	Time point	Research focus	Findings	Method
Single time point studies
Licht (2004)24	Diverse CHD	23	Preop. first surgery	iCBF assessment	Periventricular leukomalacia (in 28% of patients) was associated with decreased iCBF. No evidence for sign. difference in iCBF for different CHD types. Baseline iCBF was inversely and linearly associated with hemoglobin concentration.	PASL
				Effect of hypercarbia on iCBF	Periventricular leukomalacia was associated with poor iCBF reactivity under hypercarbia.
					No evidence for sign. difference in CO2 reactivity for different CHD types.
Wang (2006)18	Diverse CHD	3	Preop. first surgery	Effect of hypercarbia on iCBF	Increase of iCBF with hypercarbia in CHD neonates.	PASL, pCASL
	Healthy controls	1
Durduran (2010)37	HLHS, TGA	12	Preop. first surgery	Effect of hypercarbia on iCBF	Increase of iCBF with hypercarbia.	PASL
Jain (2014)22	Diverse CHD	32	Preop. first surgery	Effect of hypercarbia on iCBF and iCMRO2	Increase in iCBF and decrease in oxygen extraction fraction with hypercarbia. No change in iCMRO2 with hypercarbia.	PC
Nagaraj (2015)19	Diverse CHD	43	Preop. first surgery	Global and regional iCBF in CHD subgroups vs. healthy controls	Average mean global and regional iCBF did not differ between CHD (all patients) and controls. Subgroup analyses: - single ventricle CHD have sign. lower iCBF than controls (global and regional in basal ganglia). No evidence for difference in global or regional iCBF between single ventricle and biventricular CHD. - cyanotic CHD have sign. lower regional iCBF in thalamus than controls. Cyanotic CHD have sign. lower iCBF in thalamus, basal ganglia and occipital white matter than non-cyanotic CHD. - aortic arch obstruction CHD’s have higher global and regional (basal ganglia, frontal and occipital white matter, thalami) iCBF than those without aortic arch obstruction. - CHD neonates ventilated on admission have sign. higher global and regional occipital white matter iCBF than non-ventilated CHD. - no relationship between gestational age at birth, lowest oxygen saturation, and SNAP score with CBF. - patients that had fetal cerebroplacental ratio <1 have sign. higher global and regional BG iCBF than those with cerebroplacental ratio >1. - CHD with antenatal increased isthmus flow have increased regional OWM iCBF than those without. - CHD with antenatal increased MCA RI have lower iCBF in OWM than controls.	pCASL
	Healthy controls	58
Wintermark (2015)20	Atrioventricular canal defect	1	Preop. first surgery	Regional iCBF in CHD vs. control	iCBF in white matter was sign. increased in patient with atrioventricular canal defect vs. healthy controls. iCBF in cortical grey matter and basal ganglia did not differ sign. between atrioventricular canal defect patient and healthy controls.	PASL
	Healthy controls	3
Fogel (2015)38	HLHS/single ventricle	34	Preop. stage II surgery	Correlation CBF and aortopulmonal shunt flow	Strong inverse correlation between CBF and APC/shunt flow on room air.	PC (cardiac)
				Effect of hypercarbia on CBF	Strong inverse correlation between CBF and APC/shunt flow with hypercarbia. This inverse relationship was stronger under hypercarbia than on room air. CBF as % of aortic flow increased under hypercarbia.
Lim (2016)21	Diverse CHD	32	Preop. first surgery	CBF/iCBF and CDO2/iCDO2 in CHD vs. control	CBF and iCBF: no sign. difference in CHD vs. controls. CDO2 and iCDO2 in CHD is sign. lower than in controls. Age-dependent increase of CBF and iCBF is not sign. different btw CHD and controls. Age-dependent increase of CDO2 and iCDO2 is sign. different btw CHD and controls. Subgroup analysis: sign. lower CDO2 in single ventricle and TGA than in controls/no s. difference CoA and controls). Sign. correlation CDO2/iCDO2 and total maturation score. Sign. correlation CDO2 and total brain volume. No association between white matter changes and CBF or CDO2.	PC
	Healthy controls	31
Fogel (2017)42	Diverse CHD	63	Preop. stage II surgery	Correlation of iCBF and cerebral oxygen delivery with brain lesions	CBF indexed to aortic flow (PC), CBF indexed to brain volume (PC) and iCBF (ASL) were not associated with brain lesions preop. to stage II. No sign. effect of cerebral oxygen delivery on brain abnormalities.	pCASL and PC (cardiac)
				Effect of hypercarbia on CBF	No sign. effect of CO2 reactivity on the odds of observing brain abnormalities.
Kelly (2017)26	Diverse CHD	24	Preop. first surgery	Correlation of CDO2/iCDO2 and brain volumes/gyrification index	CDO2 correlates with brain volume (total and grey matter) and gyrification index. Indexing CDO2 per unit of brain volume weakened both the association with grey matter volume and gyrification index. Subgroup analysis: trend to lower iCBF and iCDO2 in CHD with left-sided and abnormal mixing lesions than in CHD with right-sided lesions. CDO2 sign. correlates with CBF but not with arterial saturation.	PC
Kelly (2019)23	Diverse CHD	39	Preop. first surgery	Correlation of CDO2 and microanatomical structure (diffusion-weighted imaging)	Linear relationship CDO2 and cortical orientation dispersion indices across many cortical regions. No evidence for sign. correlation of CBF or saturation alone with orientation dispersion indices. Absolute CBF for subgroups provided. Highest CBF in patients with pulmonary atresia, lowest CBF in patients with tricuspid atresia.	PC
Ng (2020)25	Diverse CHD	49	Preop. first surgery	Correlation of CDO2 and voxel-wise brain structure (tensor-based morphometry)	No sign. association between voxel-wise brain structure and CBF or CDO2. No sign. differences in CBF or CDO2 between cardiac subgroups (abnormal mixing vs. left-sided vs. right-sided lesions). Sign. positive correlation between CDO2 and total brain, cortical grey matter, and deep grey matter volumes.	PC
Bonthrone (2021)41	Diverse CHD	53	Preop. first surgery	Correlation of CDO2 and brain tissue atypicality indices	Sign. positive correlation of CDO2 with all brain tissue volume atypicality indices (total tissue volume, cortical grey matter, white matter, cerebellum, brainstem, left/right caudate, left/right lentiform nucleus, and left/right thalamus).	PC
					No evidence for sign. correlation of CDO2 with ventricle or extracerebral cerebrospinal fluid atypicality indices.
				Correlation of CDO2 and neurodevelopmental outcome	No evidence for sign. correlation of CDO2 with neurodevelopmental outcome at 22 months (Bayley III).
					Reduced CDO2 is indirectly associated with poor cognitive outcomes through the mediating effect of reduced volumetric brain development in several brain lesions.

APC/shunt aortic-to-pulmonary collateral or aortic-to-pulmonary shunt, ASL arterial spin labeling, CBF cerebral blood flow, CDO₂ cerebral oxygen delivery, CHD congenital heart disease, CO₂ carbon dioxide, DCS diffuse correlation spectroscopy, HLHS hypoplastic left heart syndrome, iCBF indexed cerebral blood flow, iCDO₂ indexed cerebral oxygen delivery, iCMRO₂ cerebral metabolic rate of oxygen consumption, MCA middle cerebral artery, PASL pulsed ASL, pCASL pseudocontinuous ASL, PC phase contrast, Preop. preoperative, sign. significant, TBM tensor-based morphometry, TGA transposition of great arteries.