The use of functional imaging in the diagnosis of carotid patch infection.

Carotid patch infection following carotid patch angioplasty is a rare but serious complication. Accurate diagnosis is vital yet currently ill-defined. We present the use of computed tomography positron emission tomography and leucocyte radioisotope scintigraphy and highlight their potential role in the diagnosis of equivocal carotid patch infection.

FDG and FDG-labelled leucocyte PET/CT in the imaging of prosthetic joint infection.

PURPOSE: The demand for arthroplasty is rapidly growing as a result of the ageing of the population. Although complications such as heterotrophic ossification, fracture and dislocation are relatively rare, differentiating aseptic loosening, the most common complication of arthroplasty from infection, is a major challenge for clinicians. Radionuclide imaging is currently the imaging modality of choice since it is not affected by orthopaedic hardware. Whereas FDG PET/CT imaging has been widely used in periprosthetic infection, it cannot discriminate aseptic from septic inflammation. In this study we aimed to evaluate the role of FDG PET/CT and FDG-labelled leucocyte PET/CT in the diagnosis of periprosthetic infection. METHODS: Of 54 patients with painful joint arthroplasty who were imaged by FDG PET/CT for diagnosis of periprosthetic infection examined, 46 (36 women, 10 men; mean age 61.04 ± 12.2 years, range 32-89 years) with 54 painful joint prostheses (19 hip, 35 knee) with grade 2 (above liver uptake) FDG accumulation on FDG PET/CT were included in the study and these 46 patients also underwent FDG-labelled leucocyte PET/CT. Final diagnoses were made by histopathological-microbiological culture or clinical follow-up. RESULTS: The final diagnosis showed infection in 15 (28%) and aseptic loosening in 39 (72%) of the 54 prostheses. FDG PET/CT was found to have a positive predictive value of 28% (15/54). Since patients with no FDG uptake on FDG PET/CT were excluded from the study, the sensitivity, specificity, negative predictive value and accuracy could not be calculated. The sensitivity, specificity, and positive and negative predictive values of FDG-labelled leucocyte PET/CT were 93.3% (14/15), 97.4% (38/39), 93.3% and 97.4%, respectively. CONCLUSION: Since FDG is not specific to infection, the specificity of FDG PET/CT was very low. FDG-labelled leucocyte PET/CT with its high specificity may be a useful method and better than labelled leucocyte scintigraphy in periprosthetic infection imaging.

Image acquisition and interpretation criteria for 99mTc-HMPAO-labelled white blood cell scintigraphy: results of a multicentre study.

PURPOSE: There is no consensus yet on the best protocol for planar image acquisition and interpretation of radiolabelled white blood cell (WBC) scintigraphy. This may account for differences in reported diagnostic accuracy amongst different centres. METHODS: This was a multicentre retrospective study analysing 235 WBC scans divided into two groups. The first group of scans (105 patients) were acquired with a fixed-time acquisition protocol and the second group (130 patients) were acquired with a decay time-corrected acquisition protocol. Planar images were interpreted both qualitatively and semiquantitatively. Three blinded readers analysed the images. RESULTS: The most accurate imaging acquisition protocol comprised image acquisition at 3 - 4 h and at 20 - 24 h in time mode with acquisition times corrected for isotope decay. CONCLUSION: Using this protocol, visual analysis had high sensitivity and specificity in the diagnosis of infection. Semiquantitative analysis could be used in doubtful cases, with no cut-off for the percentage increase in radiolabelled WBC over time, as a criterion to define a positive scan.

Usefulness of adding SPECT/CT to 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing prosthetic joint infections.

OBJECTIVE: This study evaluated the usefulness of adding single-photon emission computed tomography (SPECT)/computed tomography (CT) (SPECT/CT) to technetium Tc 99m (Tc) hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing infections in hip or knee joint prostheses. METHODS: The Tc-HMPAO-labeled leukocyte scans of 164 patients (71 with hip prostheses and 93 with knee prostheses) with clinically suspected prosthetic infections were reviewed retrospectively. Planar images were taken 4 to 6 and 21 to 26 hours after injecting the labeled leukocytes and SPECT/CT images were obtained 4 to 6 hours after the injection. The final diagnosis of infection was based on pathologic findings (n = 70), bacteriological data (n = 61), or clinical follow-up (n = 33). RESULTS: Of the 164 patients, 89 patients had a diagnosis of prosthetic joint infections. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the planar images alone were 82.0%, 88.0%, 89.0%, 80.5%, and 84.8%, respectively. When the planar images were combined with SPECT, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 91.0%, 88.0%, 90.0%, 89.2%, and 89.6%, respectively. When the planar images were combined with SPECT/CT, these values increased further to 93.3%, 93.3%, 94.3%, 92.1%, and 93.3%, respectively. Adding CT to SPECT resulted in a greater increase in sensitivity and specificity for hip prosthesis infections than for knee prosthesis infections. SPECT/CT mainly contributed by precisely localizing the anatomical site of the active inflammatory lesion and by delineating the extent of the lesion after diagnosis with SPECT. CONCLUSIONS: Single-photon emission computed tomography/CT combined with Tc-HMPAO-labeled leukocyte imaging was useful for diagnosing prosthesis infections, particularly in hip prosthesis infections, as it improved diagnostic accuracy and provided anatomical localization data.

Radiolabelled white blood cell scintigraphy in the work-up of dermal filler complications.

PURPOSE: Scintigraphy with radiolabelled autologous white blood cells (WBC) is a widely used method for the detection of sites of infection. In this study we evaluated the role of WBC scintigraphy in the diagnosis and follow-up of patients with suspected soft tissue infection caused by dermal fillers in the face. We compared several qualitative and quantitative interpretation criteria and the results obtained with MRI and high-frequency US (HFUS). METHODS: Between 2007 and 2011, ten consecutive patients (all women) aged between 25 and 65 years showing a reaction to dermal fillers were enrolled in the study. In five of these patients WBC scintigraphy was repeated at the end of therapy. Scintigraphy with (99m)Tc-HMPAO-labelled WBC was performed in each patient acquiring planar and SPECT images at 3 h and 20 h as well as HFUS with Doppler analysis and MRI with Gd-DTPA. The final diagnosis was determined by fine-needle aspiration and microbiological analysis of lesions in eight patients (before therapy in six and after therapy in two) and by clinical data and follow-up (at least 1 year) in seven patients (before therapy in four and after therapy in three). Two patients were treated with steroids, and the others were treated with antibiotics for 3 weeks. Several qualitative and semiquantitative interpretation criteria were applied to define the best strategy for accurate diagnosis of infections, implemented by SPECT images in patients with doubtful planar scans. The WBC scintigraphy results were also compared with the MRI and HFUS results. RESULTS: Sensitivity, specificity and accuracy were respectively 90 %, 100 % and 93.3 % for WBC scintigraphy with qualitative and semiquantitative interpretation of planar images and 100 %, 100 % and 100 % with qualitative analysis of SPECT images. Sensitivity, specificity and accuracy for HFUS were 44 %, 66 % and 50 %, and for MRI were 50 %, 100 % and 67.6 %, respectively. Scans performed after therapy in five patients were negative in three and still positive in two (all true results). CONCLUSION: In conclusion, scintigraphy with radiolabelled WBC was found to be the most accurate method for diagnosing infection in patients with long-term dermal filler complications, particularly using qualitative analysis of SPECT images. No differences were observed with planar images using either qualitative or semiquantitative analysis. HFUS and MRI may provide additional important information for defining the nature of the filler and for surgery, but are not accurate enough for diagnosing infection.

A large retrospective single-centre study to define the best image acquisition protocols and interpretation criteria for white blood cell scintigraphy with 99mTc-HMPAO-labelled leucocytes in musculoskeletal infections.

PURPOSE: The diagnosis of infection is often based on clinical, pathological and microbiological results. However, these investigations lack specificity. White blood cell (WBC) scintigraphy is considered the gold standard nuclear imaging technique for diagnosing infections in bone and soft tissues (except spondylodiscitis). However, image acquisition and interpretation criteria differ amongst centres throughout the world, leading to differences in reported results. The aim of this study was to identify the most accurate WBC scintigraphy acquisition and interpretation protocols for diagnosis of bone and soft tissue infections. METHODS: Included in this retrospective study were 297 patients with suspected bone or soft tissue infection who underwent WBC scintigraphy with (99m)Tc-HMPAO-labelled leucocytes between 2009 and 2012. Sensitivity, specificity, accuracy, and positive and negative predictive values of WBC scintigraphy were determined for two different dual time point acquisition protocols (fixed-time acquisition and time decay-corrected acquisition) and five image interpretation methods (visual and semiquantitative with four different reference regions of interest). Final diagnosis was based on pathological and microbiological reports, and when these were not available, on clinical follow-up of at least 6 months. RESULTS: The best acquisition protocol was 4 h and 20 - 24 h dual time-point acquisition with time decay-corrected acquisition. When using this acquisition protocol, visual qualitative interpretation led to a sensitivity of 85.1 %, a specificity of 97.1 %, a diagnostic accuracy of 94.5 %, a positive predictive value of 88.8 % and a negative predictive value of 95.9 %. For semiquantitative analysis, the best results were found when lesion-to-reference ratios were calculated with the contralateral side as the reference tissue, except for osteomyelitis and infected osteosynthesis, for which the contralateral bone marrow was found to be the best reference tissue. Results of the semiquantitative analyses per se were not better than for visual analysis. In the optimal analysis protocol, scans are first visually evaluated, and if this gives equivocal results, semiquantitative analysis is performed. This strategy resulted in an improved sensitivity of 97.9 %, a specificity of 91.8 % and a diagnostic accuracy of 93.1 %. CONCLUSION: WBC scintigraphy for bone and soft-tissue infection is best performed using a dual acquisition protocol at 4 h and at 20-24 h after injection, in which the acquisition time of the scans is corrected for decay. In most patients, visual analysis is sufficient and leads to high diagnostic accuracy. When interpretation by visual analysis is inconclusive, semiquantitative analysis adds accuracy. Based on our results, we propose a flow chart for analysing WBC scintigraphy in musculoskeletal infections.

Leukocyte and bacteria imaging in prosthetic joint infection.

There has been a significant increase in the number of joint prosthesis replacements worldwide. Although relatively uncommon, complications can occur with the most serious being an infection. Various radiological and nuclear imaging techniques are available to diagnose prosthetic joint infections (PJI). In this review article, we describe the pathophysiology of PJI, the principles of nuclear medicine imaging and the differences between Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The value of nuclear medicine techniques for clinical practice is also discussed. Then we provide an overview of the most often used radionuclide imaging techniques that may be helpful in diagnosing prosthetic joint infection: the (67)Ga-citrate, labelled white blood cells in vitro and in vivo (monoclonal antibodies directed against specific targets on the leukocytes), and (18)F-fluorodeoxyglucose ((18)F-FDG). We describe their working methods, the pitfalls, and the interpretation criteria. Furthermore, we review recent advances in imaging bacteria, a molecular imaging method that holds promises for the detection of occult infections. We conclude proposing two diagnostic flow-charts, based on data in the literature, that could help the clinicians to choose the best nuclear imaging method when they have a patient with suspicion of or with proven PJI.

Comparison of 18F-fluoro-deoxy-glucose, 18F-fluoro-methyl-choline, and 18F-DPA714 for positron-emission tomography imaging of leukocyte accumulation in the aortic wall of experimental abdominal aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a frequent form of atherothrombotic disease, whose natural history is to enlarge and rupture. Indicators other than AAA diameter would be useful for preventive surgery decision-making, including positron-emission tomography (PET) methods permitting visualization of aortic wall leukocyte activation relevant to prognostic AAA evaluation. In this study, we compare three PET tracers of activated leukocytes, 18F-fluoro-deoxy-glucose (FDG), 18F-fluoro-methyl-choline (FCH), and 18F-DPA714 (a peripheral benzodiazepine receptor antagonist) for in vivo PET quantification of aortic wall inflammation in rat experimental AAAs, in correlation with histopathological studies of lesions. METHODS: AAAs were induced by orthotopic implantation of decellularized guinea pig abdominal aorta in 46 Lewis rats. FDG-PET (n = 20), FCH-PET (n = 8), or both (n = 12) were performed 2 weeks to 4 months after the graft, 1 hour after tracer injection (30 MBq). Six rats (one of which had FDG-PET) underwent 18F-DPA714-PET. Rats were sacrificed after imaging; AAAs and normal thoracic aortas were cut into axial sections for quantitative autoradiography and histologic studies, including ED1 (macrophages) and CD8 T lymphocyte immunostaining. Ex vivo staining of AAAs and thoracic aortas with 18F-DPA714 and unlabeled competitors was performed. RESULTS: AAAs developed in 35 out of 46 cases. FCH uptake in AAAs was lower than that of FDG in all cases on imaging, with lower AAA-to-background maximal standardized uptake value (SUV(max)) ratios (1.78 ± 0.40 vs 2.71 ± 0.54; P < .01 for SUV(max) ratios), and lower AAA-to-normal aorta activity ratios on autoradiography (3.52 ± 1.26 vs 8.55 ± 4.23; P < .005). FDG AAA-to-background SUV(max) ratios correlated with the intensity of CD8 + ED1 staining (r = .76; P < .03). FCH AAA-to-background SUV(max) ratios correlated with the intensity of ED1 staining (r = .80; P < .03). 18F-DPA714 uptake was similar in AAAs and in normal aortas, both in vivo and ex vivo. CONCLUSIONS: In rat experimental AAA, characterized by an important aortic wall leukocytes activity, FDG-PET showed higher sensitivity than FCH-PET and 18F-DPA714-PET to detect activated leukocytes. This enhances potential interest of this tracer for prognostic evaluation of AAA in patients.

White blood cell SPECT during active period of cluster headache and in remission.

BACKGROUND AND PURPOSE: Cluster headache (CH) is an episodic headache disorder characterized by recurrent, unilateral attacks of excruciating pain in the temporal/orbital region. The pathophysiology of CH is largely unknown although involvement of immunological mechanisms has been suggested. The aim of our study was to investigate whether patients with CH show signs of intracranial inflammation, when using white blood cell single-photon emission computer tomography (WBC-SPECT). METHODS: We have examined 14 patients with CH, both in active period and in remission, and five control subjects at one occasion, with WBC-SPECT. To be able to precisely define regions of interest (ROI:s) in the brain, all patients with CH and control subjects underwent magnetic resonance imaging (MRI) of the brain. RESULTS: We found no significant difference in (99m)Tc-labeled WBC uptake between patients with CH in active period and controls. Furthermore, patients with CH in active period were not significantly different in uptake compared with patients with CH in remission. CONCLUSIONS: These results did not provide conclusive support for a hypothesis of a pathophysiological role of inflammation intracranially. Our conclusions are restricted to the advantages and limitations of the chosen method.

CT and MRI early vessel signs reflect clot composition in acute stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke. METHODS: Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi. RESULTS: Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P=0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P=0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P=0.002). Mean percent RBC was greater with BA (42% versus 23%, P=0.011). CONCLUSIONS: CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

99mTc-besilesomab (Scintimun) in peripheral osteomyelitis: comparison with 99mTc-labelled white blood cells.

PURPOSE: The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun) with (99m)Tc-labelled white blood cells in patients with peripheral osteomyelitis. METHODS: A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received (99m)Tc-besilesomab and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. RESULTS: The agreement in diagnosis across all three readers between Scintimun and (99m)Tc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun had higher sensitivity than (99m)Tc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). CONCLUSION: Scintimun imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to (99m)Tc-HMPAO-labelled WBCs.

[Radionuclide methods for diagnostics of non-rheumatic myocarditis and postmyocarditic cardiosclerosis].

We compared the results of comprehensive scintigraphic examination of 35 patients with suspected myocarditis and the data of clinical, immunological, laboratory and instrumental studies. The patients were divided into 3 groups. Group 1 included 11 patients with preliminary diagnosis of acute myocarditis, group 2--11 patients with chronic myocarditis, group 3--13 patients with postmyocarditic cardiosclerosis. All patients were tested for antimyocardial antibodies, underwent 99mTc-HMPAO-labeled leukocyte and perfusion scintiography of myocardium. The study did not reveal significant differences between the three groups as regards the results of laboratory and instrumental studies. Elevated titers of antimyocardial antibodies were found in 70% of the patients in group 1, 100% in group 2, and 46% in group 3. Patients with chronic myocarditis had the highest titers of antibodies. Pathological accumulation of 99mTc-HMPAO-labeled leukocytes in myocardium was documented in 36.4 and 81.8% of the patients of groups 1 and 2 respectively. They were absent in the heart of group 3 patients. Disturbed myocardial perfusion was recorded in 45.5, 81.8 and 84.6% in groups 1, 2 and 3 respectively. The magnitude of accumulation of leukocytes was not significantly different between the groups. Results of the study suggest rather high specificity of radionuclide techniques for diagnostics of inflammatory lesions in myocardium. However, further studies are needed to confirm their sensitivity and accuracy.

Can calcification predict 131I accumulation on metastatic lymph nodes in papillary thyroid carcinoma patients receiving 131I therapy? Comparison of CT, 131I WBS and 18F-FDG PET/CT.

OBJECTIVE: The aim of this study was to clarify the predictive significance of nodal calcification in terms of the therapeutic option of (131)I therapy in papillary thyroid carcinoma (PTC) patients. METHODS: We reviewed 19 computed tomography (CT) examinations of PTC patients on receiving (131)I therapy for the presence of nodal calcification, and compared the (131)I whole-body scintigraphy and (18)F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT findings. The metastatic lymph nodes (mLNs) were divided into three groups: A, those with calcification; B, those without calcification but belonging to patients who had calcified mLNs; C, those without calcification and belonging to patients who had no calcified mLNs. The incidences of (131)I accumulation and maximum standardised uptake values (SUV max) in the three groups were compared. RESULTS: A total of 70 mLNs were evaluated. Twelve mLNs belonged to group A, 13 to group B and 45 to group C. The incidences of (131)I accumulation were significantly higher in groups A (100%) and B (100%) than in group C (11.1%) (p < 0.0001 for both). The SUVmax was significantly lower in groups A (4.1 +/- 1.9) and B (3.9 +/- 1.4) than in group C (7.1 +/- 4.4) (p = 0.01, p = 0.002, respectively). CONCLUSIONS: Our results indicated that calcification in mLNs related to the ability of (131)I accumulation and less dedifferentiation.

Discordance between labelled white blood cell scintigraphy and bone scan following suspicion of bone infection: what should be done about it?

BACKGROUND: Bone infection is a common issue in infectiology. The gold standard for evaluating bone infection is the white blood cell (WBC) scan. In our practice the WBC scan is coupled with a bone scan. Discordances in the results of these two examinations are a common occurrence in daily practice. We decided to investigate the meaning of these discordances. MATERIALS AND METHODS: Two hundred and ninety-six 99mTc-HMPA labelled white blood cells (WBC) and 99mTc-HMDP bone scanning (BS) examinations were performed in our department between 1997 and 2003 for evaluation of bone infection. Out of these 296 examinations, a first rating extracted 54 scans that were considered discordant. These 54 scans were reviewed by three observers. Clinical and paraclinical data were obtained for all the cases definitely considered as discordant by all three observers. RESULTS: The observers finally retained 18 cases as discordant from the initial 296 (6.1%). Thirteen patients were not infected,and five patients were considered infected based on clinical follow-up or bacteriological and histological data. For the 17 patients with WBC-, BS+, 4 (23.5%) were infected. CONCLUSION: Our study shows that in the vast majority(17 out of 18), discordances consist of a negative WBC scan with a positive bone scan. In these cases the accuracy of the WBC scan is diminished as 23.5% of the patients with a negative WBC and a positive bone scan are infected.

Diabetic foot infection: usefulness of SPECT/CT for 99mTc-HMPAO-labeled leukocyte imaging.

UNLABELLED: Our aim was to evaluate the role of SPECT/CT for the diagnosis of diabetic foot infection by labeled leukocytes. METHODS: Seventeen patients with 19 clinically suspected sites of infection were included. After leukocyte labeling and administration, planar scans were acquired at 30 min, 4 h, and 24 h for 18 consecutive patients. SPECT/CT was obtained at 6 h. The final diagnosis was established by clinical follow-up (24 mo) in all cases and by bone biopsy for 14 sites. RESULTS: Leukocyte scanning was positive in 16 of 19 lesions and negative in 3. SPECT/CT changed the interpretation of the planar and SPECT images for 10 of 19 suspected sites (52.6%): it excluded osteomyelitis in 6 cases, revealed bone infection in 1 case, and revealed both bone and soft-tissue infection in 3 cases. The hybrid device did not significantly contribute to the evaluation of patients with negative scan results. CONCLUSION: SPECT/CT can be useful for a more accurate diagnosis of diabetic foot infection by labeled leukocyte imaging.

Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct.

Inflammatory responses after myocardial infarction profoundly impact tissue repair. Yet, efficient tools to serially and noninvasively assess cellular and molecular functions in postinfarct inflammation are lacking. Here we use multichannel fluorescent molecular tomography (FMT) for spatiotemporal resolution of phagocytic and proteolytic activities mediated by macrophages and neutrophils in murine infarcts. We performed FMT imaging to compare the course of efficient and impaired healing in wild-type and FXIII-/- mice, respectively. Mice subjected to coronary ligation received simultaneous injections with Prosense-680, an activatable fluorescence sensor reporting on cathepsin activity, and CLIO-VT750, a magneto-fluorescent nanoparticle for imaging of phagocyte recruitment. On FMT, Prosense-680 infarct signal was 19-fold higher than background (P<0.05). Protease activity was higher in the infarcted lateral wall than in the remote, uninjured septum on ex vivo fluorescence reflectance imaging (contrast to noise ratio 118+/-24). CLIO-VT750 FMT signal coregistered with contrast enhancement in the hypokinetic infarct on MRI. Microscopic fluorescence signal colocalized with immunoreactive staining for cathepsin, macrophages and neutrophils. Flow cytometry of digested infarcts revealed monocytes/macrophages and neutrophils as the source of the fluorescence signal. Phagocytic activity peaked on day 6, and proteolytic activity peaked on day 4 after myocardial infarction. FMT detected impaired recruitment of phagocytes and protease activity in FXIII-/- mice (P<0.05). FMT is a promising noninvasive molecular imaging approach to characterize infarct healing. Spectrally resolved imaging agents allow for simultaneous assesment of key processes of in vivo cellular functions. Specifically, we show that in vivo FMT detects impaired healing in FXIII-/- mice.