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Reduced Perfusion in Pulmonary Infiltrates of High-risk Hematologic Patients Is a Possible Discriminator of Pulmonary Angioinvasive Mycosis

Posted Jun 30, 2012 Updated Apr 10, 2023
By Maximilian Schulze MD , Wichard Vogel MD , Daniel Spira MD , Alexer Sauter MD , Juergen Hetzel MD , Marius Horger MD
12 min read

Rationale and Objectives

The aim of this study was to assess perfusion parameters in atypical pneumonia of heavily immunocompromised hematologic patients suspected of having invasive mycosis using volume perfusion computed tomography and establish their diagnostic role.

Materials and Methods

Volume perfusion computed tomographic data from 21 consecutive immunocompromised patients presenting with atypical parenchymal opacity of consolidation were analyzed with respect to the degree of perfusion of their pneumonias. All patients presented with clinical and laboratory signs of infection. Seventeen patients (10 men, seven women; mean age, 57 years; age range, 19–76 years) were found with proven ( n = 9), probable ( n = 2), or possible ( n = 6) angioinvasive mycosis. One patient was diagnosed with bronchoinvasive aspergillosis. Four patients (all men; mean age, 71 years; age range, 67–79 years) were diagnosed with bacterial pneumonia. Volume perfusion computed tomography of the involved pulmonary areas was performed at 80 kV and 60 mAs, with 26 measurement points distributed over 65.9 seconds. Fifty milliliters of contrast material was injected at a rate of 5 mL/s, followed by a 50-mL saline chaser. Entire coverage of the pneumonic parenchymal consolidation was obtained in all patients, with the generation of parametric maps of blood flow (BF) using the maximal slope model and blood volume (BV) using Patlak analysis. The results of perfusion measurements were then analyzed and evaluated for all patients.

Results

Patients with proven, probable, or possible angioinvasive pulmonary fungal infection revealed very low levels of perfusion of their parenchymal consolidations, with BFs ranging from 0.01 to 23.86 mL/100 mL tissue/min and BVs ranging from 0.88 to 10.67 mL/100 mL tissue, lower than those of the adjacent thoracic musculature and of bacterial pneumonias. Bacterial pneumonias showed all increased perfusion parameters, with BFs ranging from 30.49 to 41.65 mL/100 mL tissue/min and BVs ranging from 10.07 to 49.90 mL/100 mL tissue. The cutoff BF value for differentiation was 23.89 mL/100 mL tissue/min, and the cutoff BV value was 9.6 mL/100 mL tissue.

Conclusions

Patients with angioinvasive pulmonary mycosis showed lower perfusion parameters on volume perfusion computed tomography compared to those experiencing bacterial pneumonia.

Patients with hematologic and oncologic malignant diseases necessitating high-dose chemotherapy with or without subsequent stem cell transplantation are at high risk for infections of the respiratory system. Among them, the pulmonary mycoses are the most devastating infectious complications . Despite introduction of antimycotic prophylaxis, the incidence of proven and probable fungal infections can still reach 24% among patients with leukemia . Mortality from fungal infections in immunocompromised hematologic patients depends on their extent (localized vs disseminated) and organisms’ aggressiveness and ranges between 40% and 50% in invasive pulmonary aspergillosis, rising up to ≥70% for fusariosis and mucormycosis . Prophylaxis strategy with posaconazole in patients with acute myelogenous leukemia (AML) or graft-versus-host-disease can be considered an effective treatment strategy by preventing invasive aspergillosis and reducing the rate of death related to fungal infections . However, the diagnosis of breakthrough fungal infections represents a new challenge to radiologists and has substantial importance for patient outcomes and health system costs.

Diagnostic confirmation of invasive pulmonary mycosis is often difficult, and definitive diagnosis must be made by histologic studies. Noninvasive radiologic diagnosis generally requires high-resolution computed tomographic (HRCT) imaging of the chest, which is superior to conventional chest radiography but is often also nonspecific .

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Materials and methods

Patients

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Table 1

Patients Characteristics, Validation, and Laboratory Data

Patient Type of Pneumonia EORTC Classification Age Gender Underlying Disease Histology ANC (×1000/μL) ∗ Ag +/− Therapy Outcome 1 Fungal Proven 61 M CMML-2 Mucormycosis 0.02 − Amphotericin B Relapse 2 Fungal Proven 49 M Hairy cell leukemia_Candida albicans_ 0.08 − Amphotericin B Death § 3 Fungal Proven 56 F AML_Absidia_ spp 0.06 − Amphotericin B Survival 4 Fungal Proven 56 M CLL Aspergillosis 1.11 NA Voriconazole Death § 5 Fungal Proven 59 F MCL Aspergillosis 0.01 + † Voriconazole Survival 6 Fungal Proven 19 M ALL Aspergillosis 0.68 Voriconazole, amphotericin B Survival 7 Fungal Proven 69 M B-NHL Aspergillosis 1.1 + Voriconazole Survival 8 Fungal Proven 64 M IMF Aspergillosis (PCR positive) 0.16 + Voriconazole Therapy resistant 9 Fungal Probable 63 F AML NA 0.01 + † Voriconazole No therapy 10 Fungal Probable 71 M AML NA 0.1 + Amphotericin Death § 11 Fungal Possible 64 M ALL NA 0.01 + ‡ Amphotericin Relapse 12 Fungal Possible 62 F AML NA 0.01 + ‡ Voriconazole Relapse 13 Fungal Possible 76 F AML NA 0.04 − Voriconazole Death § 14 Fungal Possible 45 F MDS NA 0.29 − Amphotericin B Death § 15 Fungal Possible 31 M AML NA 0.01 − Voriconazole Relapse 16 Fungal Possible 20 F ALL NA 0.01 − Voriconazole Survival 17 Fungal Proven 55 M AML Bronchoinvasive aspergillosis 0.87 + † None Survival 18 Bacterial 79 M PC_Streptococcus_ Leukocytosis NA Amoxicillin clavulanate Survival 19 Bacterial 67 M AML_Actinomyces_ (BAL) Leukocytes normal NA Cefuroxime, doxycycline, trimethoprim/sulfamethoxazole Survival 20 Bacterial 68 M MDS_Pneumococcus_ (blood culture) 0.43 − Trimethoprim/sulfamethoxazole, clarithromycin, amoxicillin clavulanate Survival 21 Bacterial 69 M AML_Escherichia coli_ Leukocytosis − Piperacillin/tazobactam, clarithromycin Survival

ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ANC, absolute neutrophil count; BAL, bronchoalveolar lavage; B-NHL, B-cell non-Hodgkin’s lymphoma; CLL, chronic lymphatic leukemia; CMML-2, chronic monocytic myelogenous leukemia; EORTC, European Organisation for Research and Treatment of Cancer; IMF, idiopathic myelofibrosis; MCL, mantle cell lymphoma; MDS, myelodysplastic syndrome; NA, not assigned; PC, prostate cancer.

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CT Protocol

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Image Analysis

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Statistical Analysis

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Results

Standard Morphologic Chest HRCT Analysis

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Table 2

High-resolution Computed Tomographic Findings in Angioinvasive Pulmonary Mycosis (Patients 1–16), Bronchoinvasive Mycosis (Patient 17), and Bacterial Pneumonias (Patients 18–21)

Patient Location Size (mm) Hypodense Sign Halo-Sign Airspace Bronchogram Nodular Shape Wedge Shape Polygonal Shape 1 LRL 77 − − − − + − ULL 22 + − − + − − 2 LRL 52 − + + − + − LLL 40 − + + − + − LRL 12 − + − + − − 3 Lingula 89 − − + − + − 4 LLL 19 − + − + − − LLL 62 + − + − + − LRL 34 − + + − − + LRL 57 − − + − + − 5 ULL 10 − + − + − − 6 LLL 32 − − − + − − LRL 20 − + − + − − URL 5 − − − + − − 7 URL 44 + − + − − + ULL 34 − + + − − + 8 URL 13 + + − + − − 9 LLL 90 − − + − + − LLL 15 − + − + − − 10 ULL 58 + − − − + − 11 ULL 51 − − + − − + 12 ULL 11 − + − + − − 13 Lingula 33 + + − − + − 14 ULL 56 + − − + − − 15 ULL 14 − + − − + − 16 ULL 42 + + + − − + 17 ULL 15 − + − + − − LLL 10 − + − + − − URL 8 − + − + − − LRL 8 − + − + − − 18 ULL 58 − − − − − − 19 LRL 90 − − + − − + 20 ULL 63 − − + − − + 21 MRL 92 − − + − + −

LLL, lower left lobe; LRL, lower right lobe; MRL, middle right lobe; ULL, upper left lobe.

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Table 3

Sensitivity and Specificity for Morphologic Radiologic Sign and VPCT Imaging Detecting Invasive Fungal Pneumonia

Hypodense Sign Halo Sign Airspace Bronchogram Nodular Shape Wedge Shape Polygonal Shape VPCT BF < 24 mL/100 mL tissue/min VPCT BV < 10 mL/100 mL/min Sensitivity 26.6% 60% 36.6% 50% 33.3% 16.6% 100% 90.6% Specificity 100% 100% 25% 100% 75% 50% 100% 100%

BF, blood flow; BV, blood volume; VPCT, volume perfusion computed tomographic.

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VPCT Analysis

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Table 4

Computed Tomographic Perfusion Measurement in Invasive Mycotic Parenchymal Opacity of Consolidation (Patients 1–17) and Bacterial Parenchymal Opacity of Consolidation (Patients 18–21)

Patient Location BF (mL/100 mL tissue/min) BV (mL/100 mL tissue) Mycotic lung infiltrates 1 LRL 0.01 3.16 ULL 0.1 3.84 2 LRL 9.02 4.1 LLL 0.37 3.26 LRL 1.98 0.88 3 Lingula 10.36 3.64 4 LLL 0.01 10.67 LLL 0.73 5.43 LRL 0.61 1.93 LRL 0.00 10.10 5 ULL 1.45 2.32 6 LLL 1.32 2.56 LRL 2.34 3.67 URL 1.87 1.98 7 URL 14.94 3.9 ULL 14.93 9.6 8 URL 0.01 3.99 9 LLL 2.35 1.33 LLL 0.01 1.89 10 ULL 6.77 1.74 11 ULL 2.08 1.61 12 ULL 3.08 3.48 13 Lingula 7.59 3.09 14 ULL 5.45 2.55 15 ULL 4.83 1.78 16 ULL 5.47 5.91 17 LLL 23.86 3.56 Minimum 0.01 0.88 25th percentile 0.49 1.96 Median 2.08 3.26 75th percentile 6.12 3.95 Maximum 23.86 10.67 Mean 4.50 3.78 Standard deviation 5.82 2.58 Bacterial lung infiltrates 18 ULL 30.49 10.07 19 LRL 41.65 17.81 20 ULL 31.80 13.60 21 MRL 31.20 49.90 Minimum 30.49 10.07 25th percentile 31.02 12.71 Median 31.50 15.70 75th percentile 34.26 25.83 Maximum 41.65 49.90 Mean 33.79 22.85 Standard deviation 5.27 18.31

BF, blood flow; BV, blood volume; LLL, lower left lobe; LRL, lower right lobe; MRL, middle right lobe; ULL, upper left lobe.

Figure 1, A 76-year-old female patient with acute myelogenous leukemia and antibiotic-resistant fever in severe neutropenia without microbiologic diagnosis. A solitary wedge-shaped parenchymal opacity of consolidation extending peripherally up to the pleural lining is seen in the medial lingular segment ( arrow ) (a) . There is no positive air bronchogram. The blood flow perfusion color map shows no measurable perfusion, comparable to that in the adjacent chest wall muscles (b) .

Figure 2, A 63-year-old female patient with acute myelogenous leukemia in severe neutropenia. The patient presented with fever, cough and pulmonary rales (no microbiologic diagnosis). On thin-slice chest computed tomography, a large wedge-shaped parenchymal opacity of consolidation extending into the chest wall was found (a) . Corresponding blood flow and blood volume color maps revealed large pneumonic area with a nonperfused core ( arrow ) and slightly perfused peripheral rim ( arrowheads ) (b,c) . Infiltration of the chest wall shows reactive rim of perfusion contrary to the pulmonary consolidation. This is presumed to be caused by the more abundant and multiple feeder arterial supply of the musculature compared to the lung, in which vascularization follows mainly a centrifugal pattern.

Figure 3, A 56-year-old female patient with acute myelogenous leukemia in severe neutropenia. Thin-slice chest computed tomography was performed because of persistent fever and cough despite antibiotic prophylaxis (a) . A polygonal-shaped parenchymal opacity of consolidation due to infection with Absidia spp was found in the middle lobe ( arrow ), presenting a positive air bronchogram at its edges. On blood flow and blood volume color maps, three pulmonary areas with no measurable perfusion ( arrows ) representing infarction and necrosis are displayed, well demarcated by adjacent areas of hyperemia due to compressive atelectasis (b,c) ( arrowheads ).

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Figure 4, A 79-year-old male oncology patient developing fever in severe neutropenia due to streptococcal pneumonia. A wedge-shaped parenchymal opacity of consolidation is seen on thin-slice chest computed tomography in the left upper lobe near to the pulmonary hilus. Note increased perfusion on both blood flow (a) and blood volume (b) color maps ( arrow ).

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Discussion

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Conclusions

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References

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Academic Radiology, Volume 19, Issue 7
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