Imperial College London

Andreas A. Roussakis, MD, PhD, AFHEA

Faculty of MedicineNational Heart & Lung Institute

Clinical Project Manager
 
 
 
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Contact

 

+44 (0)20 7594 6822a.roussakis Website

 
 
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Location

 

514ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

47 results found

Mohamed MA, Zeng Z, Gennaro M, Lao-Kaim N, Myers J, Calsolaro V, Femminella G, Tyacke R, Martin-Bastida A, Gunn R, Nutt D, Edison P, Piccini P, Roussakis Aet al., 2022, Astrogliosis in aging and Parkinson’s disease dementia: a new clinical study with 11C-BU99008 PET/CT, Brain Communications, ISSN: 2632-1297

The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites (I2BS) represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an I2BS-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls (HCs) andpatients with established Parkinson’s disease dementia (PDD).Eighteen HCs (age: 45−78 years) and six patients with PDD (age: 64−77 years) had one 11C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3T MRI brain scan to facilitate the analysis of the PET-CT data and to capture individual cerebral atrophy. Regional 11C-BU99008 volumes of distribution (VT) were calculated for each subject by two-tissue compartmental modelling.Positive correlations between 11C-BU99008 VT values and age were found for all tested regions across the brain within HCs (p<0.05); furthermore, multiple regression indicated that aging affects 11C-BU99008 VT values in a region-specific manner. Independent samples t-test indicated that there was no significant group difference in 11C-BU99008 VT values betweenPDD (n=6; mean age = 71.97±4.66 years) and older HCs (n=9; mean age = 71.90±5.51 years).Our dataset shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, 11C-BU99008 PET cannot differentiate patients with PDD from healthy controls of similar age.

Journal article

Wilkins M, McKie M, Law M, Roussakis AA, Harbaum L, Church C, Coghlan JG, Condliffe R, Howard L, Kiely D, Lordan J, Rothman A, Suntharalingam J, Toshner M, Wort J, Villar SSet al., 2021, EXPRESS: Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH): A phase I/II design comprising dose finding and single arm efficacy Short title: Imatinib for PAH, Pulmonary Circulation, Vol: 11, Pages: 1-12, ISSN: 2045-8940

Pulmonary arterial hypertension is an unmet clinical need. Imatinib, a tyrosine kinase inhibitor, 200 to 400 mg daily reduces pulmonary artery pressure and increases functional capacity in this patient group, but is generally poorly tolerated at the higher dose. We have designed an open-label, single-arm clinical study to investigate whether there is a tolerated dose of imatinib that can be better targeted to patients who will benefit. The study consists of two parts. Part 1 seeks to identify the best tolerated dose of Imatinib in the range from 100 and up to 400 mg using a Bayesian Continuous Reassessment Method. Part 2 will measure efficacy after 24 weeks treatment with the best tolerated dose using a Simon’s two-stage design. The primary efficacy endpoint is a binary variable. For patients with a baseline pulmonary vascular resistance (PVR) >1000 dynes · s · cm−5, success is defined by an absolute reduction in PVR of ≥300 dynes · s · cm−5 at 24 weeks. For patients with a baseline PVR ≤1000 dynes · s · cm−5, success is a 30% reduction in PVR at 24 weeks. PVR will also be evaluated as a continuous variable by genotype as an exploratory analysis. Evaluating the response to that dose by genotype may inform a prospective biomarker-driven study.

Journal article

Hannaway N, Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, Howard J, Wall MB, Loane C, Barker RA, Piccini Pet al., 2021, Longitudinal changes in movement-related functional MRI activity in Parkinson's disease patients, PARKINSONISM & RELATED DISORDERS, Vol: 87, Pages: 61-69, ISSN: 1353-8020

Journal article

Zeng Z, Roussakis A-A, Lao-Kaim NP, Piccini Pet al., 2020, Astrocytes in Parkinson's disease: from preclinical assays to in vivo imaging and therapeutic probes, NEUROBIOLOGY OF AGING, Vol: 95, Pages: 264-270, ISSN: 0197-4580

Journal article

Porter E, Roussakis A-A, Lao-Kaim NP, Piccini Pet al., 2020, Multimodal dopamine transporter (DAT) imaging and magnetic resonance imaging (MRI) to characterise early Parkinson's disease, PARKINSONISM & RELATED DISORDERS, Vol: 79, Pages: 26-33, ISSN: 1353-8020

Journal article

Roussakis A-A, Zeng Z, Lao-Kaim NP, Martin-Bastida A, Piccini Pet al., 2020, Parkinson's disease laterality: a(11)C-PE2I PET imaging study, JOURNAL OF NEUROLOGY, Vol: 268, Pages: 582-589, ISSN: 0340-5354

Journal article

Roussakis AA, Gennaro M, Gordon MF, Reilmann R, Borowsky B, Rynkowski G, Savola JM, Hayden MR, Gunn R, Tabrizi S, Piccini Pet al., 2020, A longitudinal PET study to assess the state of microglia activation in a Phase 2 study of Laquinimod as a treatment for Huntington's disease (LEGATO-HD), Movement-Disorder-Society (MDS) International Virtual Congress, Publisher: WILEY, Pages: S102-S102, ISSN: 0885-3185

Conference paper

Jenkins P, Roussakis A-A, De Simoni S, Bourke N, Fleminger J, Cole J, Piccini P, Sharp Det al., 2020, Distinct dopaminergic abnormalities in traumatic brain injury and Parkinson’s disease, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 91, Pages: 631-637, ISSN: 0022-3050

Objective: Traumatic brain injury (TBI) and REM behavioural disorder (RBD) are risk factors for Parkinson’s disease (PD). Dopaminergic abnormalities are often seen after TBI, but patients usually lack parkinsonian features. We test whether TBI, PD and RBD have distinct striatal dopamine abnormalities using dopamine transporter imaging. Methods: 123I-ioflupane SPECT scans were used in a cross-sectional study to measure dopamine transporter (DaT) levels in moderate/severe TBI, healthy controls, early PD and RBD patients. Caudate and putamen DaT, putamen-to-caudate ratios and left-right symmetry of DaT were compared.Results: 108 participants (43 TBI, 26 PD, 8 RBD, 31 controls) were assessed. Early PD patients scored significantly higher on the UPDRS motor subscale than other groups. TBI and PD patients had reduced DaT levels in the caudate (12.2% and 18.7% respectively) and putamen (9.0% and 42.6% respectively) compared to controls. RBD patients had reduced DaT levels in the putamen (12.8%) but not in the caudate compared to controls. PD and TBI patients showed distinct patterns of DaT reduction, with PD patients showing a lower putamen-to-caudate ratio. DaT asymmetry was greater in the PD group than other groups. Conclusions: The results show that early PD and TBI patients have distinct patterns of striatal dopamine abnormalities. Early PD and moderate/severe TBI patients showed similar reductions in caudate DaT binding, but PD patients showed a greater reduction in putamen DaT and a lower putamen-to-caudate ratio. The results suggest that parkinsonian motor signs are absent in these TBI patients because of relatively intact putaminal dopamine levels.

Journal article

Roussakis A-A, Patel NH, Gennaro M, Bowen C, Phillips J, Piccini Pet al., 2020, The role of semi-quantification of 123I-FP-CIT SPECT scans in improving the quality of reporting, 6th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 973-973, ISSN: 1351-5101

Conference paper

Li W, Lao-Kaim NP, Roussakis A-A, Martin-Bastida A, Valle-Guzman N, Paul G, Soreq E, Daws RE, Foltynie T, Barker RA, Hampshire A, Piccini Pet al., 2020, Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease, NEUROIMAGE-CLINICAL, Vol: 28, ISSN: 2213-1582

Journal article

Roussakis A, Towey D, Gennaro M, Lao-Kaim N, Piccini Pet al., 2019, Parkinson’s disease dyskinesias possibly relate to greater dopamine transporter losses in the putamen over time, Journal of Neurology & Experimental Neuroscience, Vol: 5, Pages: S6-S11, ISSN: 2469-407X

The pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease is incompletely understood. This study was designed to investigate in Parkinson’s patients, whether time-related changes in striatal dopamine transporter availability are associated to the appearance of dyskinesias. 15 Parkinson’s patients had dopamine transporter-specific SPECT imaging with 123I-FP-CIT twice: at baseline (when they were drug naïve) and at follow-up (6.31±2.29 years from baseline), and were followed up clinically every six months. At the end of the study, patients were divided in two groups according to whether they had developed dyskinesias or not. Semi-quantification of 123I-FP-CIT data was performed using the occipital cortex as the reference region. Specific binding ratios were calculated for the putamen and the caudate. During the clinical follow-up, all Parkinson’s patients were treated pharmaceutically. 8 patients developed dyskinesias, while 7 remained nondyskinetic. At baseline, the two groups had similar 123I-FP-CIT specific binding ratio values for the putamen and the caudate (p>0.05). Also, between-group differences in age, disease duration, and Hoehn & Yahr scores were not statistically significant. Over-time, the putaminal 123I-FP-CIT specific binding ratio values in the dyskinetic group decreased significantly (p<0.01). The nondyskinetic patients had smaller reductions (p<0.05) during the same period of time. At follow-up, the dyskinetic patients had significantly higher Hoehn & Yahr scores (p<0.01) and were taking higher levodopa equivalent doses (p<0.001), as compared to the nondyskinetic patients. The development of Parkinson’s dyskinesias is related to a faster progression rate, as reflected by marked putaminal dopamine transporter decreases.

Journal article

Roussakis A, Lao-Kaim N, Piccini P, 2019, Brain imaging and impulse control disorders in Parkinson’s disease, Current Neurology and Neuroscience Reports, Vol: 19, ISSN: 1528-4042

Purpose of reviewParkinson’s disease (PD) has a wide spectrum of symptoms including the presence of psychiatric disease. At present, most treatment plans, comprised of dopaminergic drugs, are chronic and complex. Though dopaminergic agents are quite efficient in managing the motor aspects of the disease, chronic pharmacotherapy specifically with dopamine receptor agonists has been highly linked to the occurrence of Impulse Compulsive disorder (ICD), which can be problematic for individual patients.Recent findingsMuch of what is known today about PD-related ICD stems from brain imaging studies, however, evidence is not quite conclusive. Research in the field has been focused on identifying the underlying mechanisms of PD-related ICD and understanding the functions of the structures involved in the reward network. SummaryThis article presents an update of recent findings from key neuroimaging studies in PD-related ICD, discusses results from controversial studies, and identifies areas for future research in the field.

Journal article

Hannaway N, Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, Howard J, Wall MB, Loane C, Barker RA, Piccini Pet al., 2019, Functional responses to joystick movements during Parkinson's disease progression: a longitudinal fMRI study, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 227-227, ISSN: 1351-5101

Conference paper

Roussakis A-A, Mohamed MA, Myers J, Tyacke R, Calsolaro V, Femminella GD, Edison P, Nutt DJ, Piccini Pet al., 2019, Astrogliosis in Parkinson's disease dementia: a preliminary report with brain, 5th Congress of the European-Academy-of-Neurology (EAN)

Poster

Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, Searle G, Xing Y, Gunn R, Schwarz ST, Auer DP, Piccini P, Barker Ret al., 2019, Multimodal imaging of neuromelanin and dopamine transporters in Parkinson's disease reveals asymmetrical relationships within the nigrostriatal system, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 99-99, ISSN: 1351-5101

Conference paper

Martin Bastida A, Lao-Kaim N, Roussakis A, Searle G, Xing Y, Gunn R, Schwarz S, Barker R, Auer D, Piccini Pet al., 2019, Relationship between neuromelanin and dopamine terminals within the parkinson’s nigrostriatal system, Brain, Vol: 142, Pages: 2023-2036, ISSN: 1460-2156

Parkinson’s disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterising its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we utilised neuromelanin-sensitive magnetic resonance imaging and the highly specific dopamine transporter positron emission tomography radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson’s disease. Fifteen healthy controls also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal/ventral tiers and striatal nuclei into pre/post-commissural sub-regions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson’s disease subjects displayed reduced neuromelanin levels in the ventral (-30±28%) and dorsal tiers (-21±24%) as compared to the control group (F1,43 = 11.95, P = 0.001). Within the Parkinson’s disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier (F1,29 = 36.19, P < 0.001) and lower in the clinically-defined most affected side (F1,29 = 4.85, P = 0.036). Similarly, lower dopamine transporter density was observed in the ventral tier (F1,29 = 76.39, P < 0.001) and clinically-defined most affected side (F1,29 = 4.21, P = 0.049). Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-d

Journal article

Roussakis A, Gennaro M, Lao-Kaim N, Towey D, Piccini Pet al., 2019, Dopamine transporter density in de novo Parkinson’s disease does not relate to the development of levodopa-induced dyskinesias, Journal of Neuroinflammation and Neurodegenerative Diseases, Vol: 3

Background: In Parkinson’s disease (PD), the onset of levodopa-induced dyskinesias (LIDs) is difficult to predict. This study examines whether dopamine transporter (DAT)-specific SPECT imaging in de novo PD relates to later development of LIDs.Methods: 42 de novo unilateral PD participants received DAT-specific SPECT imaging with 123I-FP-CIT at time of diagnosis. At five years post-diagnosis, all PD patients were clinically evaluated and divided into two groups based on whether they had or had not developed LIDs. Fourteen gender- and age-matched healthy volunteers undertook 123I-FP-CIT SPECT imaging and were included as controls. A semi-quantification approach was used for the 123I-FP-CIT data using the occipital cortex as the reference region. We calculated specific binding ratios (SBR) for the caudate and putamen (posterior and anterior putaminal subregions). In parallel, we analysed our 123I-FP-CIT dataset with a voxel-based analysis approach.Results: PD patients had significantly lower striatal 123I-FP-CIT SBR values in comparison to controls (p<0.001). After five years, dyskinetic patients (N=10) were taking higher daily doses of dopaminergic medication (p<0.001) and had more severe disease (difference in Hoehn & Yahr staging scores p<0.05) as compared to the nondyskinetic group (N=32). At the time of diagnosis, 123I-FP-CIT SBR values were not statistically different between the two groups for all striatal regions (p>0.05). SPM voxel-based analysis did not show a statistically significant difference between the two groups (p>0.05).Conclusion: 123I-FP-CIT SPECT imaging, performed at diagnosis in de novo early-stage PD could not differentiate patients who will develop LIDs within five years from those who will not.

Journal article

Martin-Bastida A, Lao-Kaim N, Pietracupa S, Wall M, Roussakis A, Xing Y, Schwarz S, Auer D, Piccini Pet al., 2018, Assessing working memory dysfunction with letter n-back functional MRI task in early-stage Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S688-S688, ISSN: 0885-3185

Conference paper

Martin-Bastida A, Lao-Kaim N, Pietracupa S, Roussakis A, Xing Y, Schwarz S, Auer D, Piccini Pet al., 2018, Compensatory functional activations in early-stage Parkinson's disease: A cross-sectional motor planning fMRI study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S653-S653, ISSN: 0885-3185

Conference paper

Li W, Lao-Kaim N, Roussakis A, Martin-Bastida A, Valle-Guzman N, Paul G, Soreq E, Daws R, Foltynie T, Barker R, Hampshire A, Piccini Pet al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: A resting-state fMRI and 11C-PE2I PET imaging study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S682-S683, ISSN: 0885-3185

Conference paper

Roussakis AA, Lao-Kaim N, Martin-Bastida A, Piccini Pet al., 2018, A longitudinal PET study to assess progression of laterality in Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S690-S690, ISSN: 0885-3185

Conference paper

Roussakis A, Piccini P, 2018, Molecular imaging of neuroinflammation in idiopathic Parkinson's Disease, International Review of Neurobiology, Vol: 141, Pages: 347-363, ISSN: 0074-7742

Neuroinflammation is an important aspect of Parkinson's disease. The study of Parkinson's disease neuroinflammation is quite challenging and is accompanied by controversy. To date, molecular imaging studies have been targeting microglia and more recently astrocytes. In this review article, we discuss the findings from key PET studies with tracers specific for the translocator protein (microglia-specific) and novel evidence from the development of astrocyte-specific PET tracers. We also discuss evidence from pathology studies and in the animal model of Parkinson's disease that form the biological background of current and newer PET neuroinflammation tracers. However, findings from PET imaging studies in microglia have so far not been translated in clinical practice, while no PET study has been conducted in Parkinson's disease specifically targeting astrocytes. Research work is currently focused on (a) identifying new molecular targets for the study of neuroinflammation through PET, (b) assessing the state of neuroinflammation in Parkinson's disease with accuracy and reliability, and (c) developing strategies to modulate the underlying processes of neuroinflammation.

Journal article

Li W, Lao-Kaim NP, Roussakis A, Martin-Bastida A, Valle-Guzman N, Paul G, Soreq E, Daws RE, Foltynie T, Barker R, Hampshire A, Piccini Pet al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: a resting-state fMRI and 11C-PE2I PET imaging study, 4th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 345-345, ISSN: 1351-5101

Conference paper

Martin-Bastida A, Lao-Kaim NP, Xing Y, Loane C, Roussakis AA, Schwarz ST, Foltynie T, Barker RA, Auer DP, Piccini Pet al., 2017, NIGRAL IRON SUSCEPTIBILITY IN PARKINSON'S DISEASE: A LONGITUDINAL STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A34-A35, ISSN: 0022-3050

Conference paper

Li W, Lao-Kaim N, Roussakis AA, Martin Bastida A, Valle Guzman N, Paul G, Loane C, Widner H, Politis M, Foltynie T, Barker R, Piccini Pet al., 2017, 11C-PE2I and 18F-DOPA PET for assessing progression rate in Parkinson’s: a longitudinal study, Movement Disorders, Vol: 33, Pages: 117-127, ISSN: 0885-3185

Background18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD.MethodsThirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months.ResultsStandard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal Δ11C-PE2I BPND, ΔUPDRS-III, and Δbradykinesia-rigidity, whereas no significant associations were found for Δ18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between Δ11C-PE2I BPND and Δbradykinesia-rigidity.ConclusionsStriatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 Interna

Journal article

Li W, Lao-Kaim NP, Roussakis A, Martin-Bastida A, Loane C, Valle-Guzman N, Kefalopoulou Z, Politis M, Foltynie T, Barker RA, Piccini Pet al., 2017, Longitudinal comparison of 11C-PE2I and 18F-DOPA pet for assessing severity and rate of disease progression in patients with Parkinson's disease, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 128-128, ISSN: 0022-510X

Conference paper

Roussakis AA, Towey D, Piccini P, 2017, Longitudinal single-photon emitted computed tomography (SPECT) study of striatal dopamine transporter (DAT) density: Relevance to levodopa-induced dyskinesias in Parkinson's disease, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 949-949, ISSN: 0022-510X

Conference paper

Li W, Lao-Kaim N, Roussakis A, Martin-Bastida A, Valle-Guzman N, Loane C, Kefalopoulou Z, Politis M, Foltynie T, Barker R, Piccini Pet al., 2017, 11C-PE2I and 18F-DOPA PET imaging for assessing the severity and rate of progression in Parkinson's disease: The longitudinal study, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 593-593, ISSN: 1351-5101

Conference paper

Roussakis A-A, Towey D, Piccini P, 2017, Changes over time in striatal DAT availability in Parkinson's disease: Relevance to levodopa-induced dyskinesias, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 661-661, ISSN: 1351-5101

Conference paper

Bastida AM, Lao-Kaim NP, Xing Y, Loane C, Roussakis A, Schwarz ST, Li X, Valle-Guzman N, Mahlknecht P, Paul-Visse G, Widner H, Politis M, Foltynie T, Barker R, Auer DP, Piccini Pet al., 2017, Assessing longitudinal iron deposition in deep grey matter nuclei with high-pass filtered phase MR Imaging in Parkinson's disease, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 427-427, ISSN: 1351-5101

Conference paper

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