THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE British Nuclear Medicine Society – Spring Meeting Brighton 2015 THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE A Matos1, M Jessop1, AM Peters1, N Singh1, A Hosur1, V Raman1, G Keramida1, M Aplin1, S Dizdarevic1 1- Nuclear Medicine, Department of Imaging, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK April 2015

Summary Introduction Purpose Methods Results Discussion Conclusion THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Summary Introduction Purpose Methods Results Discussion Conclusion Acknowledgements References

Disclosure Statement Research Support 1: Nothing to declare. THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Disclosure Statement Research Support 1: Nothing to declare. ____________________________________________________________________________________________ ________ Consultant 2: Nothing to declare. Speakers Bureau 3: Nothing to declare. Honoraria and/or Stockholder 4,5: Nothing to declare. __________________________________________________________________________________________ _________ 1 Do you receive financial support or support in kind (e.g. free radiopharmaceuticals) from companies/institutions for your research activities? If yes, please specify for which research activity and from which company. 2 Are you acting as a consultant to any company in the field of Nuclear Medicine? If yes, please specify for which company you are acting. 3 Are you hired and paid by a speakers bureau and/or a company to hold scientific talks? If yes, please specify by which speakers bureau/company and on which subject. 4 Do you receive any other honoraria not mentioned above that you would like to disclose? If yes, please specify. 5 Do you hold shares in any companies in the field of Nuclear Medicine which would give rise to a potential conflict of interest and which you need to disclose? If yes, please specify.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Introduction Single Photon Emission Computed Tomography (SPECT) with 123I-Ioflupane is a widely available technique evaluating the integrity of nigrostriatal dopaminergic synapses which are affected in presynaptic Parkinsonian syndromes, and helpful in differentiating between Essential Tremor and Parkinsonian Syndromes (1,2). SPECT 123I-Ioflupane images have been evaluated using visual assessment or by manual regions of interest (ROIs) (3). Fig. 1 Striatal dopaminergic synapse (2) Quantification involves placing ROIs over the caudate and putamen and computing ratios to a background region. Some advantages of quantification are: more objective assessment, detection of more subtle changes and an aid to visual interpretations(3). ________________________________________________________________________________________________________________ 1- Jan Booij, et al. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. European Journal of Nuclear Medicine Vol. 28, No 3, March 2001. 2- David S.W. Djang, et al. SNM Practice Guideline for Dopamine Transporter Imaging with 123I-Ioflupane SPECT 1.0*. The Journal of Nuclear Medicine Vol. 53 No. 1, January 2012. 3- GE Healthcare. DaTQUANT* White Paper. NU-0217-05.12-EN-US DOC1156038.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Purpose The aim of the study was to assess if DAT quantification influenced confidence of reporting clinicians and final reports.

Fig. 2 DaTQUANT VOIs on a SPECT 123I-Ioflupane Image THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Methods Retrospective Study SPECT 123I-Ioflupane images Between April and November 2014 Reporting Visually Semi-quantitative analysis Transaxial images Iterative reconstruction 10 OSEM iterations, 10 subsets Butterworth post-filter The application used for quantification was DaTQUANT®, which is based on fully automated registration of the patient’s SPECT scan to the Montreal Neurological Institute MR template, calculating striatal binding and asymmetry ratios. Uptake in the striatal regions is obtained using a volume of interest (VOI) atlas in regions as, caudate, putamen (anterior and posterior), striatum and background. A score of 1-5 (1 being least) was applied to assess clinicians reporting confidence and quantification usefulness. A retrospective review of SPECT 123I-Ioflupane images was conducted in our institution between April and November 2014. All scans were reported visually and assessed by semi-quantitative analysis. Transaxial images were obtained using iterative reconstruction (10 OSEM iterations, 10 subsets) with a Butterworth post-filter. Fig. 2 DaTQUANT VOIs on a SPECT 123I-Ioflupane Image

Visual Assessment/ Quantification THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results The study included a total of 96 SPECT 123I-Ioflupane images performed in our institution. Table 1: Agreement and Disagreement between Visual Assessment and Quantification Visual Assessment/ Quantification Frequency Percentage Agreement 84 87.5% Disagreement 12 12.5% Total 96 100%

Quantification Increased Confidence THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results - Confidence Quantification increased clinicians’ confidence in 40% of the cases where there was agreement. When in agreement, majority of the cases increased clinicians’ confidence by 1 or 2. Table 2: Agreement between Visual Assessment and Quantification – Increase of Confidence Quantification Increased Confidence Frequency Percentage YES 34 40% NO 50 60% Total 84 100% Fig. 3 Agreement between Visual Assessment and Quantification – Increase of Confidence Scale (1-5)

Results – Change of diagnosis THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results – Change of diagnosis Where disagreement (12.5%), according to reporting clinicians, diagnosis would have changed in a third of these cases (33%). Table 3: Disagreement between Visual Assessment and Quantification – Change of Diagnosis Quantification Change Diagnosis Frequency Percentage YES 4 33% NO 8 67% Total 12 100% Fig. 4 Disagreement between Visual Assessment and Quantification – Change of Diagnosis

Quantification Usefulness THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results - Usefulness Quantification was shown to be useful in 60% of cases which were in agreement with visual assessment and 58% of those in disagreement. Table 4: Agreement/Disagreement between Visual Assessment and Quantification – Overall Usefulness Quantification Usefulness Frequency Percentage Total YES NO Agreement 50 34 60% 40% 84 Disagreement 7 5 58% 42% 12

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results - Usefulness Fig. 5 Agreement between Visual Assessment and Quantification – Overall Usefulness Fig. 6 Disagreement between Visual Assessment and Quantification – Overall Usefulness

Results Case 1 - 72 years old, male THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results Case 1 - 72 years old, male - ?Extrapyramidal syndrome. Left-sided slowness. History of subdural on the right in the past Fig. 7 Display of Summed Image SPECT 123I – Ioflupane Fig. 8 Analysis review screen of DaTQUANT SPECT 123I – Ioflupane Images

Results Case 2 - 57 years old, female THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results Case 2 - 57 years old, female - Suspected early Parkinson's disease Fig. 9 Display of Summed Image SPECT 123I – Ioflupane Fig. 10 Analysis review screen of DaTQUANT SPECT 123I – Ioflupane Images

Results Case 3 - 76 years old, male THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results Case 3 - 76 years old, male - Suspected Parkinson's disease; previous stroke Fig. 11 Display of Summed Image SPECT 123I – Ioflupane Fig. 12 Analysis review screen of DaTQUANT SPECT 123I – Ioflupane Images

Results Case 4 - 66 years old, male - Predominantly right-sided tremor THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results Case 4 - 66 years old, male - Predominantly right-sided tremor Fig. 13 Display of Summed Image SPECT 123I – Ioflupane Fig. 14 Analysis review screen of DaTQUANT SPECT 123I – Ioflupane Images

Results Case 5 - 69 years old, male THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Results Case 5 - 69 years old, male - ?Cognitive involvement and parkinsonism Fig. 15 Display of Summed Image SPECT 123I – Ioflupane Fig. 16 Re-processed Summed Image SPECT 123I – Ioflupane Fig. 17 Analysis review screen of DaTQUANT SPECT 123I – Ioflupane Images

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Discussion The visual assessment of most of the SPECT 123I-Ioflupane images included in the study was in agreement with quantification (DaTQUANT®) however there were cases of disagreement (12.5%). Quantification was shown to be useful in 60% of cases, when in agreement with visual assessment and useful in 58%, when in disagreement. Overall, quantification was very useful when visual assessment was equivocal. When in disagreement, in most of the cases (67%), quantification would not change the final diagnosis. Our results indicate that quantification increases the reporting confidence (40%) in the final report, mainly in borderline cases or when visual assessment is not clear.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Conclusion Quantification is a useful adjuvant tool for 123I-Ioflupane SPECT image reporting, improving reporting confidence and can impact on diagnosis.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE References 1- Jan Booij, et al. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. European Journal of Nuclear Medicine Vol. 28, No 3, March 2001. 2- David S.W. Djang, et al. SNM Practice Guideline for Dopamine Transporter Imaging with 123I-Ioflupane SPECT 1.0*. The Journal of Nuclear Medicine Vol. 53 No. 1, January 2012. 3- GE Healthcare. DaTQUANT* White Paper. NU-0217-05.12-EN-US DOC1156038.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE Acknowledgements Authors would like to thank everyone directly or indirectly involved in this study.

THE INFLUENCE OF QUANTIFICATION ON SPECT 123I-IOFLUPANE “The human brain is a wonderful organ. It starts to work as soon as you are born and doesn't stop until you get up to deliver a speech.” George Jessel