What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Radiological differentiation between bacterial orbital cellulitis and invasive fungal sino-orbital infections.

PURPOSE: Invasive fungal orbital infections (IFOI) may be difficult to differentiate from sinogenic bacterial orbital cellulitis (OC). This study investigates the features differentiating OC from IFOI on magnetic resonance imaging (MRI). METHODS: Retrospective study of adult patients with sinogenic OC and IFOI with pre-intervention MRI. Patients without post-septal involvement, non-sinogenic OC (e.g.: secondary to trauma) and poor-quality scans were excluded. Independent Sample's t test and Fisher's exact test were conducted with p < 0.05 deemed statistically significant. RESULTS: Eleven cases each of OC (Mean age: 41.6 ± 18.4 years-old, Male: 10) and IFOI (Mean age: 65.0 ± 16.6 years-old, Male: 9) between 2006 and 2023. IFOI patients were older, more likely immunocompromised and had a lower mean white-cell count (p value = 0.005, 0.035 and 0.017, respectively). The ethmoid and maxillary sinuses were most commonly involved in both entities. Pre-septal and lacrimal gland involvement were more common in OC (p = 0.001 and 0.008, respectively). Infiltrative OC orbital lesions were poorly demarcated, whilst those in IFOI were expansile/mass-like invading the orbit from the adjacent paranasal sinuses. Specific IFOI features included loss-of-contrast-enhancement (LoCE) of paranasal sinus tissues with orbital extension. Extra-orbital and -sinonasal extension indicative of IFOI included contiguous skull base or pterygopalatine fossa involvement, retro-antral and masticator space stranding and vasculitis. CONCLUSION: This study describes the key MRI features of IFOI including differentiating markers from OC. These specific features, such as LoCE of the paranasal and orbital soft tissues, the location and pattern of contiguous soft-tissue involvement, provide expedient identification of IFOI which necessitate early surgical intervention for microbiological confirmation of an invasive fungal pathology.

Radiology-based diagnosis of fungal pulmonary infections in high-risk hematology patients: are we making progress?

PURPOSE OF REVIEW: In patients with hematological malignancies, high-resolution computed tomography (CT) is the recommended imaging approach for diagnosis, staging and monitoring of invasive fungal disease (IFD) but lacks specificity. We examined the status of current imaging modalities for IFD and possibilities for more effective applications of current technology for improving the specificity of IFD diagnosis. RECENT FINDINGS: Although CT imaging recommendations for IFD are largely unchanged in the last 20 years, improvements in CT scanner technology and image processing algorithms now allow for technically adequate examinations at much lower radiation doses. CT pulmonary angiography can improve both the sensitivity and specificity of CT imaging for angioinvasive molds in both neutropenic and nonneutropenic patients, through detection of the vessel occlusion sign (VOS). MRI-based approaches also show promise not only for early detection of small nodules and alveolar hemorrhage but can also be used to detect pulmonary vascular occlusion without radiation and iodinated contrast media. 18F-fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) is increasingly used to monitor long-term treatment response for IFD, but could become a more powerful diagnostic tool with the development of fungal-specific antibody imaging tracers. SUMMARY: High-risk hematology patients have a considerable medical need for more sensitive and specific imaging approaches for IFD. This need may be addressable, in part, by better exploiting recent progress in CT/MRI imaging technology and algorithms to improve the specificity of radiological diagnosis for IFD.

The vanishing nasal septum sign: a case of severe fungal sinusitis.

Acute invasive fungal sinusitis (AIFS) is a fungal infection of the nasal cavity and paranasal sinuses with associated invasion of adjacent vessels and soft/hard tissues. It usually occurs in immunocompromised patients and may follow a rapid course of less than four weeks with high mortality rate. We report a 39-year-old male with relapse of acute myelogenous leukemia (AML) who was under evaluation for neutropenic fever. On his sinus CT, there was loss of calcification of his nasal septum when compared to a prior head CT, a sign indicative of an aggressive infectious process. He was diagnosed with AIFS and underwent emergent surgical debridement and systemic antifungal therapy, leading to a positive outcome. The sign described on CT ("Vanishing Nasal Septum" sign) may provide an additional, reliable tool to prospectively identify locally aggressive cases of invasive fungal infections of the nasal cavity at an earlier stage and improve patient outcomes.

The role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in assessment of complex invasive fungal disease and opportunistic co-infections in patients with acute leukemia prior to allogeneic hematopoietic cell transplant.

INTRODUCTION: Individuals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention. METHODS: Two distinct cases of pulmonary co-infection of rare fungal and bacterial pathogens are explored in severely immunocompromised individuals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long-term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long-term antimicrobials prior to transition to HCT. DISCUSSION: The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting. CONCLUSION: FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high-risk immunocompromised patients.

Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review.

COVID-19 patients have been found to have an increased incidence of superadded fungal infections because of multiple factors such as impaired cell-mediated immunity, immunosuppressive therapy, and coexistent diabetes mellitus. Recently, there has been a significant rise in the COVID-19-associated mucormycosis and aspergillosis cases involving the sinonasal cavity and the lungs. Rhino-orbito-cerebral acute invasive fungal rhinosinusitis (AIFR) is a potentially life-threatening, invasive fungal infection. Early diagnosis followed by prompt medical management and surgical intervention is crucial for patient survival. The role of cross-sectional imaging (CT/MRI) is not only to suggest a diagnosis of invasive fungal sinusitis but also to delineate the complete extent of disease. Mapping the extent of orbital and intracranial disease has prognostic as well as management implications, as involvement of these sites marks a worse prognosis. A stepwise approach to evaluation of imaging of AIFR along with a pictorial depiction of the key imaging findings is presented.

Chronic invasive fungal rhinosinusitis vs sinonasal squamous cell carcinoma: the differentiating value of MRI.

OBJECTIVES: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC). METHODS: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance. RESULTS: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC. CONCLUSIONS: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS. KEY POINTS: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity.

The use of imaging to identify immunocompromised children requiring biopsy for invasive fungal rhinosinusitis.

BACKGROUND AND PURPOSE: Children with severe immunocompromise due to cancer therapy or hematopoietic cell transplant are at risk both for potentially lethal invasive fungal rhinosinusitis (IFRS), and for complications associated with gold-standard biopsy diagnosis. We investigated whether early imaging could reliably identify or exclude IFRS in this population, thereby reducing unnecessary biopsy. METHODS: We reviewed clinical/laboratory data and cross-sectional imaging from 31 pediatric patients evaluated for suspicion of IFRS, 19 without (age 11.8 ± 5.4 years) and 12 with proven IFRS (age 11.9 ± 4.6 years). Imaging examinations were graded for mucosal thickening (Lund score), for fungal-specific signs (FSS) of bone destruction, extra-sinus inflammation, and nasal mucosal ulceration. Loss of contrast enhancement (LoCE) was assessed separately where possible. Clinical and imaging findings were compared with parametric or nonparametric tests as appropriate. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis. Positive (+LR) and negative likelihood ratios (-LR) and probabilities were calculated. RESULTS: Ten of 12 patients with IFRS and one of 19 without IFRS had at least one FSS on early imaging (83% sensitive, 95% specific, +LR = 15.83, -LR = 0.18; P < .001). Absolute neutrophil count (ANC) ≤ 200/mm3 was 100% sensitive and 58% specific for IFRS (+LR = 2.38, -LR = 0; P = .001). Facial pain was the only discriminating symptom of IFRS (P < .001). In a symptomatic child with ANC ≤ 200/m3 , the presence of at least one FSS indicated high (79%) probability of IFRS; absence of FSS suggested low (<4%) probability. CONCLUSION: In symptomatic, severely immunocompromised children, the presence or absence of fungal-specific imaging findings may effectively rule in or rule out early IFRS, potentially sparing some patients the risks associated with biopsy.

Gastrointestinal involvement of unusual Mucormycete Syncephalastrum racemosum in a diabetic patient with adenocarcinoma: rare case presentation with review of literature.

BACKGROUND: Mucormycosis is a serious and often fatal mycotic infection caused by members of class Mucormycetes in populations with immunologic or metabolic disorders. Though several clinical manifestations are associated with mucormycetes, gastrointestinal involvement is quite rare. CASE DESCRIPTION: We described a rare case of invasive fungal infection due to Syncephalastrum racemosum associated with gastric adenocarcinoma in a 48-year-old male patient with type II Diabetes mellitus. He presented with complaints of abdominal pain, nausea, vomiting, dyspepsia, dysphagia, loss of appetite, and weight. Histopathological examination showed broad and aseptate hyphae and culture of endoscopic biopsy tissue from pylorus and antrum yielded the fungal pathogen S. racemosum. The species was confirmed by molecular sequencing of D1/D2 region of the ribosomal DNA. The in vitro susceptibility of S. racemosum was tested by broth microdilution assay as per CLSI guidelines. The MICs suggest that the isolate was susceptible to Amphotericin B (0.25 µg/ml), Itraconazole (0.25 µg/ml) and Posaconazole (0.06 µg/ml) and showed resistance to Micafungin (>16 µg/ml). The patient was successfully treated with radical subtotal gastrectomy with lymphadenectomy and Amphotericin B antifungal therapy. There was a dilemma in concluding the pathogenicity of the isolate since; the symptoms noted were common for both gastric adenocarcinoma and mucormycosis. A review of previously reported cases on Syncephalastrum was presented in the paper with their clinical manifestations, treatment, and outcome. CONCLUSION: To the best of our knowledge, this is the first report from India on the gastrointestinal involvement of S. racemosum. Patients with immunocompromised status are more prone to mucormycotic infections, and any typical presentations should be carefully examined for their etiological agent, and appropriate species directed therapy would help in a better outcome.

Diagnosis and treatment of invasive fungal infections: looking ahead.

Improved standards of care depend on the development of new laboratory diagnostic and imaging procedures and the development of new antifungal compounds. Immunochromatography technologies have led to the development of lateral flow devices for the diagnosis of cryptococcal meningitis and invasive aspergillosis (IA). Similar devices are being developed for the detection of histoplasmosis that meet the requirements for speed (∼15 min assay time) and ease of use for point-of-care diagnostics. The evolution of molecular tools for the detection of fungal pathogens has been slow but the introduction of new nucleic acid amplification techniques appears to be helpful, for example T2Candida. An Aspergillus proximity ligation assay has been developed for a rapid near-patient bedside diagnosis of IA. CT remains the cornerstone for radiological diagnosis of invasive pulmonary fungal infections. MRI of the lungs may be performed to avoid radiation exposure. MRI with T2-weighted turbo-spin-echo sequences exhibits sensitivity and specificity approaching that of CT for the diagnosis of invasive pulmonary aspergillosis. The final part of this review looks at new approaches to drug discovery that have yielded new classes with novel mechanisms of action. There are currently two new classes of antifungal drugs in Phase 2 study for systemic invasive fungal disease and one in Phase 1. These new antifungal drugs show promise in meeting unmet needs with oral and intravenous formulations available and some with decreased potential for drug-drug interactions. Novel mechanisms of action mean these agents are not susceptible to the common resistance mechanisms seen in Candida or Aspergillus. Modification of existing antifungal susceptibility testing techniques may be required to incorporate these new compounds.

FDG PET/CT imaging in detecting and guiding management of invasive fungal infections: a retrospective comparison to conventional CT imaging.

PURPOSE: Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy. METHODS: FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment. RESULTS: Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT. CONCLUSION: FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.

Beyond biomarkers: How enhanced CT imaging can improve the diagnostic-driven management of invasive mould disease.

CT imaging remains an essential diagnostic test for identification, staging and management of invasive mould infection (IMI) in patients with hematological malignancies. Yet the limited specificity of standard CT imaging can drive excessive antifungal use in patients, especially when more definitive diagnosis cannot be established through microbiology or invasive diagnostic procedures. CT pulmonary angiography (CTPA) is a complimentary, non-invasive approach to standard CT that allows for direct visualization of pulmonary arteries inside infiltrates for signs of angioinvasion, vessel destruction and vessel occlusion. Experience from several centers that are using CTPA as part of a standard diagnostic protocol for IMI suggests that a positive vessel occlusion sign (VOS) is the most sensitive and a specific sign of IMI in both neutropenic and non-neutropenic patients. CTPA is particularly useful in patients who develop suspected breakthrough IMI during antifungal prophylaxis because, unlike serum and/or BAL galactomannan and polymerase chain reaction (PCR) testing, the sensitivity is not reduced by antifungal therapy. A negative VOS may also largely rule-out the presence of IMI, supporting earlier discontinuation of empirical therapy. Future imaging protocols for IMI in patients with hematological malignancies will likely replace standard chest X-rays in favor of early low radiation dose CT exams for screening, with characterization of the lesions by CTPA and routine follow-up using functional/metabolic imaging such as 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) to assess treatment response. Hence, enhanced CT imaging techniques can improve the diagnostic-driven management of IMI management in high-risk patients with hematological malignancies.

A Rare Case of Chromoblastomycosis in a 12-year-old boy.

Chromoblastomycosis is a chronic fungal infection of the subcutaneous tissue. The infection usually results from a traumatic injury and inoculation of the microorganism by a specific group of dematiaceous fungi, resulting in the formation of verrucous plaques. The fungi produce sclerotic or medlar bodies (also called muriform bodies or sclerotic cells) seen on direct microscopic examination of skin smears. The disease is often found in adults due to trauma. We report a case of chromoblastomycosis in a 12-year-old child in whom the infection started when he was only 4 years old with secondary involvement of bones, cartilage, tongue and palatine tonsils. The child was not immunosuppressed.

Radiation Dose Reduction by Using CT with Iterative Model Reconstruction in Patients with Pulmonary Invasive Fungal Infection.

Purpose To compare the diagnostic quality of reduced radiation dose computed tomography (CT) with iterative model reconstruction (IMR) versus that of conventional low-dose CT in patients with pulmonary invasive fungal infection. Materials and Methods This prospective observational study included 48 patients (mean age ± standard deviation, 39.9 years ± 11.3) known to have or suspected of having pulmonary invasive fungal infection between October 2016 and July 2017. Patients underwent CT with IMR (at 80 kV with 20 mA) immediately after low-dose CT (at 80 kV with automatic exposure control). Images were reconstructed by using a hybrid iterative reconstruction (HIR) algorithm and IMR. Two radiologists independently assessed subjective image quality, noise, and visibility of normal and abnormal findings by using a five-point scale. Objective measurements, including image noise, contrast-to-noise ratio (CNR), and corresponding figure of merit (FOM), were compared by using repeated-measures analysis of variance with Bonferroni post hoc tests for multiple comparisons. Results The mean effective dose was 0.3 mSv ± 0.3 for CT with IMR and 0.7 mSv ± 0.2 for low-dose CT (P < .01). When the image noise and CNR were normalized to the effective dose, CT images obtained with IMR had significantly higher FOM than did other image series (P < .0001). Subjectively, visibility of CT features of invasive fungal infection on CT scans reconstructed with IMR was rated as noninferior to that on low-dose CT scans reconstructed with HIR, except for the halo sign. Conclusion CT with IMR had approximately 60% dose reduction compared with conventional low-dose CT, with reduced noise and improved depiction of abnormal findings, in patients with pulmonary invasive fungal infection.

Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort.

Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

[A clinical analysis of children with invasive pulmonary fungal infections after biliary atresia surgery].

OBJECTIVE: To investigate the clinical features of invasive pulmonary fungal infections (IPFIs) after biliary atresia (BA) surgery and related risk factors. METHODS: A retrospective analysis was performed for the clinical data of 49 children with IPFIs after BA surgery, including clinical features, lung imaging findings, and pathogenic features. The risk factors for IPFIs after BA surgery were also analyzed. RESULTS: The most common pathogens of IPFIs after BA surgery was Candida albicans (17 strains, 45%), followed by Candida tropicalis (7 strains, 18%), Aspergillus (6 strains, 16%), Candida krusei (3 strains, 8%), Candida glabrata (3 strains, 8%), and Candida parapsilosis (2 strains, 5%). Major clinical manifestations included pyrexia, cough, and shortness of breath, as well as dyspnea in severe cases; the incidence rate of shortness of breath reached 78%, and 35% of all children had no obvious rale. The multivariate logistic regression analysis showed that age at the time of surgery, time of glucocorticoid application, cumulative time of the application of broad-spectrum antibiotics, and recurrent cholangitis were major risk factors for IPFIs after BA surgery. CONCLUSIONS: The three most common pathogens of IPFIs after BA surgery are Candida albicans, Candida tropicalis, and Aspergillus. It is important to perform surgery as early as possible, avoid recurrent cholangitis, and shorten the course of the treatment with broad-spectrum antibiotics and glucocorticoids for decreasing the risk of IPFIs.

Use of intravoxel incoherent motion diffusion-weighted MR imaging for assessment of treatment response to invasive fungal infection in the lung.

OBJECTIVES: The purpose of this study was to determine whether intravoxel incoherent motion (IVIM) -derived parameters and apparent diffusion coefficient (ADC) could act as imaging biomarkers for predicting antifungal treatment response. METHODS: Forty-six consecutive patients (mean age, 33.9 ± 13.0 y) with newly diagnosed invasive fungal infection (IFI) in the lung according to EORTC/MSG criteria were prospectively enrolled. All patients underwent diffusion-weighted magnetic resonance (MR) imaging at 3.0 T using 11 b values (0-1000 sec/mm2). ADC, pseudodiffusion coffiecient D*, perfusion fraction f, and the diffusion coefficient D were compared between patients with favourable (n=32) and unfavourable response (n=14). RESULTS: f values were significantly lower in the unfavourable response group (12.6%±4.4%) than in the favourable response group (30.2%±8.6%) (Z=4.989, P<0.001). However, the ADC, D, and D* were not significantly different between the two groups (P>0.05). Receiver operating characteristic curve analyses showed f to be a significant predictor for differentiation, with a sensitivity of 93.8% and a specificity of 92.9%. CONCLUSIONS: IVIM-MRI is potentially useful in the prediction of antifungal treatment response to patients with IFI in the lung. Our results indicate that a low perfusion fraction f may be a noninvasive imaging biomarker for unfavourable response. KEY POINTS: • Recognition of IFI indicating clinical outcome is important for treatment decision-making. • IVIM can reflect diffusion and perfusion information of IFI lesions separately. • Perfusion characteristics of IFI lesions could help differentiate treatment response. • An initial low f may predict unfavourable response in IFI.

Phellinus species: An emerging cause of refractory fungal infections in patients with X-linked chronic granulomatous disease.

Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease (CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections (IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer (ITS) sequencing. He improved with amphotericin B and isavuconazole but required haematopoietic stem cell transplantation (HSCT). We review the literature on Phellinus infections in CGD and conclude that: (i) these infections emerge on mould-active prophylaxis and are indolent; (ii) they typically cause locally destructive disease but can disseminate; (iii) diagnosis is delayed and requires molecular methods; (iv) amphotericin B is most active in vitro; and (v) treatment is protracted and requires surgery and possibly HSCT. In conclusion, Phellinus spp. are emerging pathogens in CGD. Every effort should be made to establish the diagnosis of non-Aspergillus IFIs in patients with CGD by sending tissue specimens for molecular diagnostics.

Radiologic findings of Fusarium pneumonia in neutropenic patients.

In neutropenic patients, lungs are involved in 50%-80% of cases of fusariosis, but imaging of pulmonary fusariosis has been previously described as indistinguishable from other invasive mould diseases. Our attempt was to identify a radiological pattern that may distinguish pulmonary fusariosis from other mould diseases. We examined the CT findings of nine neutropenic haematology patients with invasive fusariosis. As control group for comparison, we examined 14 invasive mould diseases (11 aspergillosis, 3 mucormycosis) in haematology patients with similar underlying disease and timing of CT imaging. Chest-CT in invasive fusariosis showed small airways (7/9) or peribronchial (5/9) infiltrates, less frequently macronodular consolidations (4/9) with hypodense sign, but without halo sign or occluded-vessel sign. The control group presented macronodular consolidations with occluded-vessel sign in all of the cases; the halo and the hypodense signs were observed, respectively, in 100% and 82% of aspergillosis, and in 67% and 100% of mucormycosis. Sinusitis was documented by CT in 7/7 fusariosis, 2/2 mucormycosis and 5/7 aspergillosis; maxillary and ethmoid sinuses were involved in 7/7 fusariosis, in most of the cases with hyperdense opacification (rarely observed in the controls). We concluded that no radiological findings can discriminate between different mould infections, but invasive fusariosis should be suspected if chest-CT demonstrates pulmonary infiltrates with the hypodense sign, but without the halo or the occluded-vessel signs. Suspicion is greater in the presence of hyperdense maxillary and ethmoid sinusitis.