Neuroimaging in Huntington’s disease

Table 1 Key positron emission tomography imaging studies in Huntington’s disease

Ref.	Subjects	PET radiopharmaceutical	Main findings
Dopaminergic system
Ginovart et al[56], 1997	5 HD patients	11C-b-CIT	50% decrease in striatal dopamine transporter (DAT) binding.
	5 HCs	11C-SCH23390 11C-raclopride	40% decrease in striatal D1 and D2 receptors binding. D1 and D2 binding in the striatum was significantly associated with the duration of symptoms
			Reduced D1 receptors binding in the temporal cortex
Bohnen et al[57], 2000	19 HD patients 64 HCs	11C-DTBZ	Reduced nigrostriatal density of VMAT2 (caudate: 33%, putamen: 56%-75%)
Sedvall et al[58], 1994	5 HD patients	11C-SCH 23390	75% reduction in striatal D1 receptor density in HD patients
	1 premanifest HD gene carrier 5 HCs		D1 binding in the premanifest HD gene carrier was in the lower range of the HCs
Turjanski et al[55], 1995	10 HD patients 9 HCs for 11C-raclopride and 6 HCs for 11C-SCH 23390	11C-SCH 2339011C-raclopride	Parallel reduction of striatal D1 and D2 receptor binding (31%-39%) with greater loss of mean striatal D1 and D2 binding in the akinetic-rigid patients than those choreic patients without rigidity
Lawrence et al[60], 1998	17 premanifest HD gene carriers	11C-SCH 23390 11C-raclopride	Correlation between striatal D1 and D2 receptors binding and cognitive performance
Pavese et al[61], 2003	12 HD patients	11C-raclopride	4.8% annual reduction in striatal D2 receptor binding
	HCs from previous studies		D2 reduction receptor density in extrastriatal regions including amygdala, temporal and frontal cortex
Andrews et al[64], 1999	9 premanifest HD gene carriers 4 HD patients	11C-SCH 23390 11C-raclopride	Mean annual loss of D1 and D2 binding of 2% and 4% respectively in the group of asymptomatic HD gene carriers
	7 HCs 3 subjects at risk for HD		Mean annual loss of D1 binding of 5% and D2 binding of 3% in symptomatic HD patients
			UHDRS motor scores and TFC correlated with PET measures of striatal dopamine receptor in both groups
			Premanifest HD gene carriers with active progression had an increased mean annual loss of D1 and D2 receptor binding (5% and 6.5% respectively)
Pavese et al[62], 2010	16 HD patients11 premanifest HD gene carriers	11C-raclopride	62.5% of symptomatic HD patients and 54.5% of premanifest carriers showed cortical reductions in D2 binding
	HCs from previous studies		HD patients with decreased cortical D2 binding had worse scores on
			neuropsychological tests assessing attention and executive functions than subjects without cortical dopamine dysfunction
Antonini et al[66], 1998	10 premanifest gene carriers 8 HD patients	11C-raclopride	Correlation between CAG repeat length and the estimated percentage loss of striatal D2 binding after age correction in premanifest HD gene carriers and HD patients
			Rate of disease progression is faster during the earlier asymptomatic stages of the disease
Brain activation and metabolism
Antonini et al[65], 1996	10 premanifest HD gene carriers	18F-FDG 11C-raclopride	Annual loss of 2.3% in striatal glucose metabolism and 6.3% annual decline in D2 receptor binding
	8 HD patients
	HCs from previous studies
Kuwert et al[75], 1990	23 HD patients 21 HCs	18F-FDG	Decreases of caudate and regional cortical metabolism correlated with cognitive decline
Ciarmiello et al[79], 2006	24 premanifest HD gene carriers47 HD patients	18F-FDG	Significant decrease in glucose uptake in the cortex (frontal and temporal lobes) and striatum in both premanifest HD gene carriers and HD patients
	30 HCs		Striatal and cortical hypometabolism in premanfest HD gene carriers precedes neuronal loss
Ciarmiello et al[80], 2012	43 premanifest HD gene carriers	18F-FDG	Premanifest HD gene carriers who phenoconverted after five years from the PET scan had a mean glucose uptake in the caudate significantly lower than the those who remained symptom-free after five years
Weeks et al[83], 1997	7 HD patients 7 HCs	H215O	Impaired activation of the striatum and its frontal motor projection areas during motor tasks such as paced joystick movements
Tang et al[87], 2013	12 premanifest HD gene carriers 12 HCs	18F-FDG 11C-raclopride	Network analysis showed a significant spatial covariance pattern characterized by progressive changes in striato-thalamic and cortical metabolic activity network activity increased linearly over 7 yr and was not influenced by intercurrent phenoconversion
Neuroinflammation and activated microglia
Pavese et al[99], 2006	11 HD patients 10 HCs	11C-PK11195 11C-raclopride	Significant microglial activation in the striatum and cortical regions of HD patients
			Striatal 11C-PK11195 binding correlates with loss of striatal dopamine D2 binding
			Striatal 11C-PK11195 binding correlated with UHDRS scores
Tai et al[100], 2007	11 premanifest HD gene carriers	11C-PK11195 11C-raclopride	Increased striatal and cortical microglial activation in premanifest HD gene carriers
	10 HCs		Higher striatal 11C-PK11195 binding correlated with lower striatal D2 binding
Politis et al[101], 2011	8 premanifest HD gene carriers 8 HCs (11C-raclopride) 8 HCs (11C-PK11195)	11C-PK11195 11C-raclopride	Increased levels of activated microglia in areas of the striatum associated with cognition and other areas related to cognitive function
			Levels of microglial activation correlated with clinical scales of disease severity and motor dysfunction and with a higher probability of HD onset over the next 5 yr
Cannabinoid system
Van Laere et al[111], 2010	20 HD patients 14 HCs	18FMK-9470	Decrease of CB1 availability throughout the gray matter of the cerebrum, cerebellum, and brain stem in HD patients.

PET: Positron emission tomography; HD: Huntington’s disease.