Introduction: Deep vein thrombosis (DVT) is a common condition associated with high morbidity and mortality related to disease and treatment complications (1). Prognostication and treatment of DVTs may benefit from an understanding of thrombus location, volume, chronicity, and the presence of embolization (2). Current diagnostic techniques rely on multiple imaging modalities such as ultrasound or contrast CT imaging, which are limited by operator and patient specific characteristics and may be unable to accurately age thrombus. Improved techniques for whole body thrombus detection, localization, volume quantification and aging, would be beneficial. We aimed to test the utility of a novel fibrin-targeted PET probe (64Cu-FBP8) in patients with DVTs of variable chronicity (3). 

Methods: In this cross-sectional pilot analysis, individuals aged >/=18 years old with lower limb venous thrombosis diagnosed by duplex ultrasound were recruited to undergo 64Cu-FBP8 Positron Emission Tomography (PET) and Magnetic Resonance (MR) imaging of the lower extremities and, in a subset of individuals, the thorax as well. Regions of interest were drawn around the major veins of the lower extremities, on consecutive axial slices, and the maximum standardized uptake value (SUVmax) was recorded from each slice. Venous territories were classified according to their position in the leg (proximal, mid or distal leg). The most diseased segment (MDS) SUVmax is the average of three consecutive SUVmax readings, centered on the highest SUVmax, for each venous territory (4). Territories not adequately captured on both PET/MR and ultrasound were excluded. The MDS SUVmax was compared between ultrasound confirmed thrombosed and non-thrombosed venous territories using a Mann-Whitney U test. Furthermore, a Jonckheere-Terpestra test was used to examine the trend in MDS SUVmax across groups of no thrombus, acute thrombus and chronic thrombus. Chronic thrombus was defined as asymptomatic thrombus, a duration of symptoms >/=45 days, or features of suggestive of chronicity on ultrasound. All other thrombi were acute. Receiver Operator Curve analysis was used to determine the area under the curve for the detection of ultrasound determined thrombus. Thoracic imaging was reviewed for evidence of embolization.

Results: Eighteen individuals undergoing 64Cu-FBP8 PET/MR of the lower limbs had a mean age of 59.6±13.7 years, and 13 (72%) were male. The mean activity of radiotracer administered was 191.1±18.4 MBq and the mean duration of time between radiotracer injection and imaging was 117.5±34.4 minutes. Sixty venous territories were adequately captured on both PET imaging and ultrasound imaging and of these, 17 territories were positive for thrombus on ultrasound (28.3%).  The median MDS SUVmax was higher in thrombosed territories compared to non-thrombosed territories (1.50 [1.29 – 2.67] v 1.30 [1.09 – 1.46], p=0.019). There was an increasing MDS SUVmax across no thrombus, chronic thrombus and acute thrombus groups (1.30 [1.09 – 1.46] v 1.43 [1.27 – 1.50] v 2.65 [1.54 – 3.26], p=0.008, Figure 1). One individual with an ultrasound confirmed acute thrombus in a left lower limb had no discernable activity seen in this region on PET imaging, though a small focus of intense activity was seen in the posterior basal segment of the right lower lobe of the lung (SUVmax 2.0), suspicious for embolization of the index DVT. The area under the curve for all thrombi (n=17), acute thrombi only (n=8), and acute thrombi without suspicion of embolization (n=7) was 0.70, 0.82 and 0.94, respectively (p<0.05 for all).

Conclusion: 64Cu-FBP8 PET/MR can identify sites of acute DVT within the lower limbs, can identify sites of embolization, and in individuals with known lower limb DVT it may help discriminate between acute and chronic thrombus. Further research is needed to determine whether this technique can improve diagnosis and prognostication, and influence treatment decisions.

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Figure 1. Uptake of 64Cu-FBP8 can be used to assess thrombus age. The most diseased segment (MDS) SUVmax values across different categories of thrombus chronicity are shown. The MDS score increased across venous territories with no thrombi, chronic thrombi and acute thrombi.

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