Alfred O. Ankrah

Imaging fungal infections in children.

Fungal infections in children rarely occur, but continue to have a high morbidity and mortality despite the development of newer antifungal agents. It is essential for these infections to be diagnosed at the earliest possible stage so appropriate treatment can be initiated promptly. The addition of high-resolution computer tomography (HR CT) has helped in early diagnosis making; however, it lacks both sensitivity and specificity. Metabolic changes precede anatomical changes and hybrid imaging with positron emission tomography (PET) integrated with imaging modalities with high anatomical resolution such as CT or magnetic resonance imaging (MRI) is likely to detect these infections at an earlier stage with higher diagnostic accuracy rates. Several authors presented papers highlighting the advantages of PET/CT in imaging fungal infections. These papers, however, usually involve a limited number of patients and mostly adults. Fungal infections behave different in children than in adults, since there are differences in epidemiology, imaging findings, and response to treatment with antifungal drugs. This paper reviews the literature and explores the use of hybrid imaging for diagnosis and therapy decision making in children with fungal infections.

Evaluation of glucose uptake by skeletal muscle tissue and subcutaneous fat in HIV-infected patients with and without lipodystrophy using FDG-PET

ObjectiveTo evaluate differences in glucose uptake by skeletal muscle tissue and subcutaneous fat in HIV patients on highly active antiretroviral therapy (HAART) presenting with and without lipodystrophy as well as in drug-naive HIV patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography. Patients and methodsThirty-nine consecutive patients suffering from HIV: seven drug-naive patients, 21 nonlipodystrophic patients on HAART and 11 patients on HAART, respectively, suffering from lipodystrophy were prospectively included. All patients underwent a whole-body FDG positron emission tomography examination. Standardized uptake values (SUV values) of muscle and subcutaneous fat were compared and related to demographic and biochemical variables. ResultsSUV mean values of subcutaneous fat were significantly higher in patients under HAART presenting with lipodystrophy when compared with untreated and treated, nonlipodystrophic patients (P=0.000). SUV mean values of subcutaneous fat significantly correlated with treatment duration (r=0.56, P=0.000) and CD4 count (r=0.51, P=0.001) and inversely correlated with viral load (r=−0.61, P=0.000). Finally, SUV mean values of thigh muscles were not significantly different between the three different patient groups under study. ConclusionQuantitative FDG uptake by subcutaneous fat proved significantly higher in HIV patients under HAART presenting with lipodystrophy. HAART did not influence FDG uptake by human skeletal muscle tissue under basal conditions.

Metabolic Imaging of Infection

Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and neoplastic tissue and then extending to more targeted probes that seek to identify specific microbial species. This focus review describes the metabolic and molecular imaging techniques currently available for clinical use in infection imaging and those that have demonstrated promising results in preclinical studies with the potential for clinical applications.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT

Emerging data from published studies are demonstrating the superiority of Ga‐68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge‐68/Ga‐68 from which Gallium‐68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head‐to‐head comparison, the diagnostic sensitivity of Ga‐68 PSMA PET/CT and Tc‐99m PSMA SPECT/CT in patients with prostate cancer.

The role of PET in monitoring therapy in fungal infections

Positron emission tomography (PET) is a powerful diagnostic nuclear medicine imaging technique. PET allows in vivo detection of a wide variety of physiologic and pathologic phenomena and it offers a noninvasive tool for the monitoring of therapy in various diseases. Invasive fungal infections (IFIs) are a global concern because of the increasing population of patients at risk of IFIs and the high morbidity and mortality. Therapy with antifungal agents is long-standing and expensive. The emerging resistant fungal strains make the management of IFIs challenging. There is an absolute need for a sensitive noninvasive biomarker capable of monitoring the disease activity of IFIs and determining the efficacy of treatment at an early time point. PET imaging with 18F-fluorodeoxyglucose (FDG) was used to detect and assess disease activity in IFI foci already over 20 years ago. At that time, it was suggested it could be a useful biomarker for monitoring antifungal therapy. However, this knowledge has still not been fully exploited for the management of IFIs. The literature reveals an increasing realization of the usefulness of PET in monitoring therapy of IFIs. In this review, we highlight the advantages of nuclear medicine techniques in the management of IFIs with emphasis of the role of PET in monitoring therapy efficacy.

Monitoring Response to Therapy

Monitoring response to treatment is a key element in the management of infectious diseases, yet controversies still persist on reliable biomarkers for noninvasive response evaluation. Considering the limitations of invasiveness of most diagnostic procedures and the issue of expression heterogeneity of pathology, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively. The usefulness of 18F-FDG-PET/CT in assessing treatment response in infectious diseases is more promising than for conventional imaging. However, there are currently no clinical criteria or recommended imaging modalities to objectively evaluate the effectiveness of antimicrobial treatment. Therapeutic effectiveness is currently gauged by the patients subjective clinical response. In this review, we present the current studies for monitoring treatment response, with a focus on Mycobacterium tuberculosis, as it remains a major worldwide cause of morbidity and mortality. The role of molecular imaging in monitoring other infections including spondylodiscitis, infected prosthetic vascular grafts, invasive fungal infections, and a parasitic disease is highlighted. The role of functional imaging in monitoring lipodystrophy associated with highly active antiretroviral therapy for human immunodeficiency virus is considered. We also discuss the key challenges and emerging data in optimizing noninvasive response evaluation.

Optimization of Ordered Subset Expectation Maximization Reconstruction for Reducing Urinary Bladder Artifacts in Single-photon Emission Computed Tomography Imaging.

Bladder artifact during bone single-photon emission computed tomography (SPECT) is a common source of error. The extent and severity of bladder artifacts have been described for filtered back projection (FBP) reconstruction. Ordered subset expectation maximization (OSEM) may help to address this problem of bladder artifacts, which render up to 20% of the SPECT images unreadable. The objective of this study was to evaluate the relationship of the bladder to acetabulum ratio in guiding the choice of the number of iterations and subsets used for OSEM reconstruction, for reducing bladder artifacts found on FBP reconstruction. One hundred five patients with various indications for bone scans were selected and planar and SPECT images were acquired. The SPECT images were reconstructed with both FBP and OSEM using four different combinations of iterations and subsets. The images were given to three experienced nuclear physicians who were blinded to the diagnosis and type of reconstruction used. They then labeled images from the best to the worst after which the data were analyzed. The bladder to acetabulum ratio for each image was determined which was then correlated with the different iterations and subsets used. The study demonstrated that reconstruction using OSEM led to better lesion detectability compared to FBP in 87.62% of cases. It further demonstrated that the iterations and subsets used for reconstruction of an image correlate with the bladder to acetabulum ratio. Four iterations and 8 subsets yielded the best results in 48.5% of the images, whilst 2 iterations and 8 subsets yielded the best results in 33.8%. The number of reconstructed images which yielded the best results with 2 iterations and 8 subsets was the same as or more than those with 4 iterations and 8 subsets when the bladder/acetabulum ratio (A/B) was between 0.2 and 0.39. A ratio below 0.2 or above 0.39 supports the usage of 4 iterations and 8 subsets over 2 iterations and 8 subsets. We conclude that bladder to acetabulum ratio can be used to select the optimum number of iterations and subsets for reconstruction of bone SPECT for accurate characterization of lesions. This study also confirms that reconstruction with OSEM (vs. FBP) leads to better lesion detectability and characterization.

The Role of Nuclear Medicine in the Staging and Management of Human Immune Deficiency Virus Infection and Associated Diseases

Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of nuclear medicine techniques, with particular emphasis of F-18 fluorodeoxyglucose, may have impact in the setting of HIV. We also provide an overview of the role of nuclear medicine techniques in the management of HIV-associated disorders.

68Ga-PSMA-HBED-CC PET/CT imaging in Black versus White South African patients with prostate carcinoma presenting with a low volume, androgen-dependent biochemical recurrence: a prospective study

Objective To compare the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/computed tomography (CT) imaging for the detection of androgen-dependent recurrent prostate carcinoma (ADPC) in Black South Africans (BSAs) versus White South Africans (WSAs) with increasing serum prostate-specific antigen (PSA) values below or equal to 10 ng/ml. Patients and methods A total of 61 patients with ADPC were prospectively included in the study (mean age: 66.7 years): 38 WSAs and 23 BSAs. 68Ga-PSMA-HBED-CC PET/CT imaging results obtained were related to serum PSA levels and to ethnicity. Results A total of 41 (67%) patients had a positive 68Ga-PSMA-HBED-CC scan result. 68Ga-PSMA-HBED-CC PET/CT positivity was significantly higher in patients with PSA values more than 2 ng/ml [32/38 (84%) patients] when compared with patients with PSA values less than 0.5 ng/ml [6/11 (55%) patients] or PSA values of 0.5–2 ng/ml [3/12 (25%) patients] (P=0.0001). Mean PSA values proved not significantly different in patients presenting with extrapelvic involvement when compared with those with intrapelvic involvement or between patients who presented with bone involvement versus those who did not on 68Ga-PSMA-HBED-CC PET/CT) (P≥0.147). Age, Gleason-scores, median PSA values, the frequency of a positive scan result, the frequency of bone involvement, and extrapelvic involvement proved similar in WSAs and BSAs (P≥0.417). Conclusion 68Ga-PSMA-HBED-CC PET/CT imaging identified a recurrence in 67% of the patients under study. Higher PSA levels were associated with 68Ga-PSMA-HBED-CC PET/CT positivity and the detection rate. Imaging results obtained proved similar in BSAs and WSAs, suggesting that the tumor burden and growth rate of ADPC are similar in both races.

Association of hemodynamic response during dipyridamole stress testing with 99mTc-MIBI SPET myocardial perfusion image findings.

The aim of this study was to assess whether there is an association between changes in the heart rate and blood pressure after dipyridamole stress and abnormal scan findings detected with gated technetium-99m methoxy isobutylisonitrile (99mTc-MIBI) myocardial perfusion imaging (MPI). A total of 200 consecutive patients with known or suspected coronary artery disease underwent MPI using a 2 days stress/rest protocol. Heart rate (HR), blood pressure and electrocardiogram were monitored during the stress study. Dipyridamole-induced increase in HR ratio (peak HR/baseline HR) of more than 1.20 and decrease in systolic blood pressure (SBP) of 10 mmHg or more were defined as a normal response. Low ejection fraction (EF) was defined as EF less than 45%. Semi-quantitative measures used include summed stress score (SSS), summed difference score (SDS), end systolic volume (ESV) and left ventricular ejection fraction (LVEF). Chi-square-and regression analysis was used to assess associations between the various hemodynamic parameters and MPI abnormalities. Our results showed that 75% of patients had abnormal scans. Statistically significant associations were observed between each of the following factors and abnormal scan findings: abnormal SBP response to dipyridamole (P=0.011), increased SSS (P=0.040) and low LVEF (P=0.012). A significant association was also observed between decreased HR response and low LVEF (P=0.012). In conclusion, this study demonstrated that an abnormal hemodynamic response during dipyridamole stress test was associated with abnormal myocardial perfusion imaging scan findings, low LVEF and SSS.