[JR1] Technetium-99m SPECTUS Hybrid Imaging Compared With Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound.pptx

Technetium-99m SPECTUS Hybrid Imaging Compared With Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

1. 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound Presenter: Randy Aliwarga Supervisor: Rd. Erwin Affandi SK, dr. , SpKN (K), MH.Kes , FANMB

2. Abstract Side-by-side evaluation of thyroid ultrasound (US) and 99m TcO4 scintigraphy can lead to uncertainties in the correct topographic assignment of thyroid nodules. The aim of this study was to evaluate 99m TcO4 single photon emission computed tomography/ultrasound (SPECT/US) fusion imaging. Seventy-nine patients were prospectively investigated. If conventional diagnostics of the thyroid gland (B-mode-US, scintigraphy) produced unclear findings, SPECT was performed and transferred to a US device for real-time sensor-navigated 3-D fusion US investigation. The data sets were manually matched according to their contours. Finally, SPECT/US versus conventional diagnostics was rated using an ordinal 4-point scale (SPECT/US >> conventional diagnostics, SPECT/US > conventional diagnostics, SPECT/US = conventional diagnostics, SPECT/US < conventional diagnostics). SPECT/US was superior (>>, >) in 84% and equivalent (=) in 16% of the cases, respectively. No statistically significant differences were observed for uni -, bi- and multinodular goiters (p 0.3). In 67%, the respective problem that arose after conventional diagnostics was clarified by SPECT/US. SPECT/US was feasible and was helpful for the clarification of uncertain functionality assessments of thyroid nodules. (E-mail: [email protected] ) © 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved. Key Words: Single-photon emission computed tomography/ultrasound, Fusion imaging, Hybrid imaging, Thyroid, Ultrasound.

3. INTRODUCTION 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

4. Background Hybrid imaging of different modalities has proven very successful in the past in overcoming the limitations of individual imaging methodologies. e.g : PET/CT and SPECT/CT have become an integral part of clinical care. Over the past 10 y, ultrasound (US) , which is widely available in clinical settings, has been tested for hybrid imaging applications. Wang, F., Nie , H., Li, W.  et al.  The clinical significance of remnant thyroid tissue in thyroidectomized differentiated thyroid cancer patients on  131 I-SPECT/CT.  BMC Med Imaging   21 , 78 (2021). https://doi.org/10.1186/s12880-021-00612-5

5. Background 99m TcO4 scintigraphy , together with high-resolution US , is a diagnostic combination that is regularly used to analyze two different imaging modalities, side-by-side , in thyroid examinations. Scintigraphy : detect and localize abnormal thyroid tissue (hyper and hypofunctional areas) Ultrasonography : detect the exact size of thyroid gland, echogenicity , and detect thyroid nodules regarding to malignancy criteria. Thyroid Scintigraphy Thyroid Ultrasonography Coronal Summation Image Axial or Sagittal Plane

6. However, … S ide-by-side analysis of both imaging modalities demands considerable spatial imagination capabilities on the part of the practitioner, because: thyroid scintigraphy is a planar summation image of a ventral view (coronal summation image) sonography is a sectional imaging modality in the axial or sagittal plane. P resence of several closely adjacent nodules or a peripheral nodule position leads to ambiguities in the assignment of scintigraphic and sonographic findings, even for experienced practitioners .

7. POSSIBLE SOLUTIONS SPECT : L imitation of (planar) scintigraphy can be circumvented with a 3-D rotating gamma cameras Overlapping and peripheral findings can be better demarcated. Do not require an additional injection of a radiopharmaceutical . Rarely used in clinical practice. Distance of detectors to thyroid gland, particularly in lateral due to shoulder. fhSPECT (free-hand SPECT) or rthESA (real-time handheld emission spot allocator) Portable Requires specialized equipment (cost problem) fhSPECT rthESA

8. AIM OF THE STUDY (1) Evaluate the technical applicability and feasibility of a new hybrid imaging approach for thyroid diagnostics. (2) Ascertain whether SPECT/US can provide additional information or clarify uncertainties of the conventional diagnostics and thus has potential to improve the diagnostic accuracy in the field of thyroid nodule characterization. (3) I nfluence of SPECT/US on therapeutic consequences has not been investigated in the present study.

9. METHODOLOGY 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

10. 0. study preparation Feb 2015 to July 2017 Local Ethic Committee (No: 4286-12/14) Written Informed Consent Declaration of Helsinki 3 INVESTIGATORS: mf, tw , ps 19 years of experience 4 years of experience Prospective study

11. 1. Conventional thyroid diagnostics

12. Inclusion criteria Complete conventional thyroid diagnostics , including: laboratory thyroid parameters thyroid US thyroid scintigraphy Unclear findings in the conventional diagnosis (unclear functionality of one/several nodules and/or unclear assignment of a distinct scintigraphic finding to several nodules) Written consent Age >18 years old Ultrasonography examination of sufficient quality

13. EXCLUSION criteria 99m TcO4 uptake <0.5% Regular use of thyroid medication Iodide exposure in the past 3 months Thyroid-stimulating hormone values below lower limit of normal range Inadequate US conditions (short neck, pronounced obesity, lack of reclinability) Sonographically detected thyroid cysts >2 cm

14. 2. SPECT & Data Conversion All included patients undergo SPECT (Siemens Symbia S ) with a 128 x 128 matrix and acquisition of 32 angles at 180° rotation, 20 seconds each. D ata were reconstructed iteratively (Flash3D) using a Gaussian filter (5.0). Total times for data acquisition and post-processing were 13 and 5 min, respectively. Data obtained with SPECT needed to be converted , as the LOGIQ E9 US instrument cannot process and display raw SPECT data. The SPECT data set was imported into PMOD software ( v. 3.409 ) and converted via DICOM interface and opened with VNAV software. After data conversion and transfer into the US instrument, the data set could be easily displayed.

15. 3. SPECT/ULTRASOUND HYBRID SPECT/US hybrid was based on sensor-navigated US. Special requirements: A special software package: VNAV (GE Electronic) Magnetic field transmitter connected to US instruments Magnetic sensors attached to US probe

16. 3. SPECT/ULTRASOUND HYBRID Alignment and co-registration with the US images were manually and subjectively performed with respect to the contours of the thyroid gland and its nodules. Since the patient is transferred onto another examination table between the SPECT and US examinations, it is almost impossible to achieve exactly the same positioning of the neck. T he recording congruency of both data sets was checked in a sagittal plane and, if required, manually adjusted so the contours of the metabolic activity and margin of thyroid gland is matched. The resulting 3-D linkage was saved; this enables real-time movement of the SPECT data set in congruence with the movements of the US transducer. I nvestigators constantly proved and re-assessed the correct alignment of SPECT and US of the thyroid gland’s contours in sagittal and transversal planes. Nodule-based appraisal by 4-point scale was carried out for 3 groups ( uni -nodular goiter, bi-nodular goiter, and multi-nodular goiter) and the differences are examined using Fisher’s exact test.

17. Defining features of the comparison of SPECT/US and conventional diagnostics Category Defining Feature SPECT/US >> Conventional The nodules are not assessable with certainty or cannot be interpreted unequivocally using conventional diagnostics . On the contrary, SPECT/US is unambiguously appraisable. The investigator is quite certain about the nodule’s functionality using conventional diagnostics , but SPECT/US reveals surprising findings . The nodule’s function is evaluated differently after SPECT/US assessment. SPECT/US > Conventional Using conventional diagnostics , the investigator has a suspicion (but is not absolutely certain) regarding genuine nodule functionality, which can be unambiguously confirmed via SPECT/US assessment SPECT/US = Conventional SPECT/US confirms the findings of an already quite certain nodule assessment using conventional diagnostic. SPECT/US does not improve or change the initial nodule assessment obtained via conventional diagnostics. SPECT/US < Conventional Conventional diagnostics reveal findings that are not depicted using SPECT/US.

18. RESULTS 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

19. Patients PROFILE Numbers of patients Multinodular Goiter Uni-nodular Goiter Bi-nodular Goiter

20. results Category All cases (n = 79) Uni-nodular Goiter (n = 11) Bi-nodular Goiter (n = 11) Multinodal Goiter (n = 57) p Value (Fisher’s exact test) SPECT/US >> Conventional 13 1 12 0.300 SPECT/US > Conventional 53 9 8 36 0.480 SPECT/US = Conventional 13 1 3 9 0.614 SPECT/US < Conventional N/A All SPECT/US examinations were successfully executed without technical problems (100%) SPECT/US was markedly superior in 16.5% cases , superior in 67.1% cases , and equivalent in 16.5% cases . There were no significant differences for these results regarding uni -nodular, bi-nodular and multinodular goiters, respectively (all p values > 0.3)

21. CASE EXAMPLES 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

22. Sixty-five-year-old female patient referred for the exclusion of cold nodules . Thyroid volume = 21 mL (right: 17 mL, left: 4 mL). Thyroid stimulating hormone = 0.6 mU /L. No thyroid autoimmune antibodies. Nodule I, right, cranial (1.3 x 2.0 x 2.1 cm, 2.7 mL), partially cystic . Nodule II right, mid-third, lateral (1.2 x 1.3 x 1.6 cm, 1.3 mL), solid , in immediate proximity to nodule I. Thyroid scintigraphy 20 min after intravenous injection of 68.3 MBq 99m TcO 4 . Technetium-99m thyroidal uptake = (right) 1.45% and (left) 0.42%. Ambiguity: Scintigraphic hypofunctionality right cranial/lateral. Which of the nodules is hypofunctional? (A) The nodules cannot be unequivocally demarcated on planar scintigraphy. A concave area of reduced uptake can be seen in the right mid-third, laterally. (B) Schematic localization of nodules ( coronal view ) based on sonographic position. (C) Schematic nodule localization ( axial view ) based on sonographic position. (D1) Nodules I ( orange arrow ) and II ( red arrow ). Sagittal ultrasound view. (D2) Single-photon emission computed tomography/ultrasound . Both the cystic portion of nodule I and the solid nodule II can be clearly classified as hypofunctional.

23. Twenty-seven-year-old female patient with a thyroid nodule on the right . Thyroid volume = 17 mL (right: 14 mL, left: 3mL). Thyroid-stimulating hormone = 3.05 mU /L. No thyroid autoimmune antibodies. Nodule I right, caudal (1.8 x 2.1 x 2.5 cm; 4.7 mL). Thyroid scintigraphy 20 min after intravenous injection of 70.0 MBq 99m TcO 4 . Technetium-99m thyroidal u ptake = (right) 0.65% and (left) 0.83%. Ambiguity: Almost symmetric representation of the thyroid gland in the scintigram. Without considering the ultrasound, normal findings. (A) Although the nodule can be indirectly intuited in the planar scintigram above an area of reduced relative uptake, it cannot be visually demarcated with certainty . (B) Schematic nodule localization ( coronal view ) based on sonographic position. (C) Schematic nodule localization ( axial view ) based on sonographic position. (D1) Nodule I: Sagittal ultrasound view. Nodule marked with orange arrow . (D2) Single-photon emission computed tomography/ultrasound. Compared with the surrounding thyroid tissue, the nodule is clearly hypometabolic and, therefore, scintigraphically cold.

24. Fifty-year-old male patient referred for the exclusion of cold nodules. Thyroid volume = 15.5ml (right: 7.5 mL, left: 8 mL). Thyroid-stimulating hormone = 1.38mU/L. No thyroid autoimmune antibodies. Nodule I left, caudal, dorsal (0.9 x 1.1 x 1.4 cm, 0.69 mL). Nodule II right, mid-third, dorsal (0.6 x 0.5 x 0.7 cm, 0.11 mL). Nodule III right, caudal, dorsal (0.8 x 0.8 x 1.0 cm, 0.32 mL). Thyroid scintigraphy 20 min after intravenous injection of 70.5 MBq 99m TcO 4 . Technetium-99m thyroidal uptake = (right) 0.38% and (left) 0.41%. Ambiguity: Scintigraphic findings almost normal. Unreliable evidence for hypo- or hyperfunctional areas. (A) The nodules cannot be demarcated with certainty using planar scintigraphy. (B) Schematic nodule position ( coronal view ) based on sonographic position. (C) Schematic nodule position ( axial view ) based on the sonographic position. (D1) Top: Axial US view . Nodule I is marked with an orange arrow . Bottom: Single-photon emission computed tomography/ultrasound. Nodule I exhibits more intense thyroid metabolism than the surrounding thyroid tissue and is therefore hypermetabolic. (D2) Top: Sagittal ultrasound view. Nodule II is marked with a red arrow . The blue arrow indicates nodule III. Bottom: Single-photon emission computed tomography/ultrasound. Nodule III ( blue arrow ) exhibits a higher uptake than the surrounding thyroid tissue and is therefore also hypermetabolic.

25. DISCUSSION 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

26. Conventional diagnostics comprising sonography and planar 99mTcO4 scintigraphy is limited, especially when several adjoining nodules are found in close proximity or in a peripheral position. This leads to uncertainties, even for experienced practitioners. Some of these diagnostic limitations can be overcomed by a 3-D acquisition of 99m TcO 4 SPECT . More accurate results than planar scintigraphy but inherently limited spatial resolution. However, it can be performed in addition to planar scintigraphy without further radiation exposure. The application of 99m TcO4-SPECT/CT is mentioned in the literature only sporadically compared to 123 I-SPECT 123 I-SPECT produce superior images, but additional radiation exposure, higher costs and limited availability. The concept of a nuclear real-time US fusion in thyroid disease was introduced in 2014 , but in conjunction with fhSPECT , in which a hand-held gamma probe with a dedicated optical tracking system is used. Apart from thyroid-related findings, initial experience so far been reported only for the localization of sentinel lymph nodes and parathyroid adenomas . Despite improved topographic representation of thyroid metabolism with SPECT, the correlation between nodules detected in sonography and their functional activity remains ambiguous in some patients. In the majority of cases, this limitation can be overcome by using SPECT/US , because the practitioner can view in real time the function of the thyroid nodule on the screen of the US instrument in a semitransparent superimposed fusion image. In 84% of patients, SPECT/US was rated as superior to conventional diagnostics.

27. Limitation Performing SPECT/US requires additional technical and personnel resources. Special software for data conversion and an US instrument with options for sensor navigation and image fusion are needed. The results presented here are based on expert assessments and not on a double-blind review . This methodology was deemed appropriate for two reasons: The approach of fusion US with 99m Tc SPECT using a conventional gamma camera has not been described with respect to thyroid diagnostics before . The appraisal was indeed performed during the SPECT/US exam and not by a second reading afterward, just like the clinical routine of regular US exams (e.g., of the thyroid, the abdomen) in which the appraisal/report is conducted during the US exam and not by reviewing the complete exam (i.e., as a video sequence) afterward. Subjective assessment of inclusion and exclusion criteria regarding conventional thyroid diagnostics (i.e., unclear findings in conventional diagnosis and inadequate US condition) may have induced human variations and even errors.

28. Limitation Since no gold standard has yet been established for verification of the correct spatial assignment of functionality to sonographically detected nodules, no quantitative analysis , including determination of sensitivity and specificity, could be carried out . Even after surgical removal of the thyroid gland and histologic processing, it is not possible to unequivocally confirm because no histologic or immunohistochemical parameter for functionality has been established. There is a selection bias with respect to the functionality of nodules, as only 10 hyperfunctional findings were recorded (data not shown). This is due to the clinical significance of hypofunctional nodules , suggesting malignancy, which require special attention and detection of hypofunctional areas pose a particular challenge in planar scintigraphy compared to hyper-functional findings. Incorrect or inaccurate registration , leading to misidentification of anatomy and metabolism and, thus, to wrong conclusions regarding a nodule’s functionality, cannot be ruled out with certainty and strongly depends on the talent and the experience of the investigator. Low-dose CT data can be an important aid in adjusting and aligning (different) image data sets but it’s not always available (as in our clinic) and add radiation exposure .

29. Limitation Although SPECT/US fusion imaging is performed in real time , data acquisition is carried out sequentially : first the SPECT data, then the US data with superimposed SPECT data. Because of different reclining angles of the head in each examination, a change in neck position is unavoidable . SPECT acquisition is contactless , but US requires slight pressure on the soft tissues of the neck , such that tissue deformation and tissue shifting lead to a lack of congruence (offset) of both data sets up to 1.5 cm (data not shown). However, this could be improved significantly in all cases with manual adjustment. Both drawbacks , the limited reproducibility of patient positioning and the slight tissue deformation by the US transducer, might be circumvented with a new methodological approach, such as using “ real-time handheld emission spot allocator ” ( rthESA ); but significant technical development is still required . In contrast, the method presented here is based on commercially available medical devices.

30. CONCLUSION 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

31. Conclusion We report that in a large group of patients, SPECT/US proved to be an applicable examination method that was always technically successful. Furthermore, it was found, based on expert assessments, that additional SPECT/US adds value and diagnostic gain in cases of unclear findings from conventional thyroid scintigraphy. SPECT/US yields a more accurate assignment of function and morphology without additional radiation exposure and within a reasonable amount of time. Future studies should address the detailed nodule-by-nodule comparison of conventional diagnostics and SPECT/US, as well as blinded analyses and inter-observer variability . Also, its therapeutic relevance should be assessed. F urther fusion US concepts, taking into consideration rthESA and PET, should be investigated.

32. THANK YOU FOR YOUR KIND ATTENTION 1 st JOURNAL READING Technetium-99m SPECT/US Hybrid Imaging Compared with Conventional Diagnostic Thyroid Imaging with Scintigraphy and Ultrasound

33. “H ybrid imaging with fhSPECT /US and 3-D 99m TcO4 scintigraphy is feasible— after overcoming technical obstacles—and might be well suited for application in routine clinical practice .” Hybrid Integration of Real-time US and Freehand SPECT: Proof of Concept in Patients with Thyroid Diseases , Martin Freesmeyer , Thomas Opfermann , and Thomas Winkens , Radiology 2014 271:3, 856-861