Introduction
Mucormycosis is an invasive fungal infection caused by the Phycomycetes group of fungi. The pathogenesis is angioinvasion.Reference Parsi, Itgampalli, Vittal and Kumar1 In addition to necrosis of tissues, it also erodes bones of the facial skeleton. Although cases of coronavirus disease 2019 (Covid-19) associated mucormycosis were reported during the first wave of Covid-19, there was an upsurge during the second wave in many cities in India, and it was declared an epidemic by various state governments. By 7 June 2021, 28 252 cases had been recorded by the Indian Ministry of Health.Reference Asrani, Eapen, Hassan and Sohal2 This increase devastated the prognosis of Covid-19 in high-risk individuals (with immunosuppression), and caused fear and apprehension in the general public. The associated mortality, poor outcomes, need for revision surgical procedures, and resultant deformities and disabilities are major concerns among healthcare personnel and the public.
The progression of Covid-19 associated mucormycosis is unpredictable, and its management is long with unclear outcomes. Coronavirus disease 2019 associated mucormycosis involves rhino-orbital-cerebral tissues, it invades deep facial structures, and it is associated with a propensity for bony infiltration and intracranial complications. The bony occurrence has been reported as a late feature, characterised by deep extension of infection through perivascular channels, resulting in evident bony destruction.Reference Silverman and Mancuso3 Resection of the entire disease, followed by restoration of cosmesis and function, is a real challenge. Facial deformity, with disturbances in swallowing, vision and speech, are points of concern for patients and clinicians.
Early diagnosis and management of Covid-19 associated mucormycosis are key to survival. The primary definitive treatment is surgical debridement, performed promptly, followed by administration of systemic antifungals. The resultant disfigurement can be addressed later on with a prosthesis. The choice of surgical approach is crucial to achieve optimal results with less morbidity, without delay. Multiple surgical procedures might be difficult in morbid patients who cannot tolerate general anaesthesia. In addition, morbidity and deformity might increase after multiple surgical procedures.
Although two-dimensional (2D) computed tomography (CT) is extensively used by otorhinolaryngologists to determine the extent of disease, a third dimension aids appreciation of the anatomy and orientation. Conventional radiography (2D CT and contrast-enhanced magnetic resonance imaging (MRI)) helps in predicting the underlying pathology to some extent. In patients with milder symptoms, it is difficult to predict the underlying damage, which might make us indecisive in choosing the correct surgical approach. Newer software and technologies help in the rapid conversion of 2D CT to three-dimensional (3D) CT images;Reference Calhoun, Kuszyk, Heath, Carley and Fishman4 in addition, these images can be created in any plane and rotated in space.Reference Chuang, Chiang, Liu and Lin5
Three-dimensional CT is performed using a helical multi-slice scanner. It is an easier and faster modality for determining the disease extent, and helps in counselling patients as well. The overlapping bones of the facial skeleton are better observed on 3D CT images, as they reveal the spatial relationship of bones and soft tissues. Three-dimensional CT can display a clear picture of disease involvement, facilitate disease staging and aid surgical decision-making. Software is used on the axial and coronal images obtained from helical 2D CT to reconstruct 3D images. The advantage of explaining the disease extent to patients and their attendants further aids in the counselling of patients.
We hereby review our experience of 3D CT used as a diagnostic aid in Covid-19 associated mucormycosis, and compare it with conventional 2D CT in terms of pre-operative evaluation and its effects on surgical management.
Materials and methods
We performed an analysis of 123 consecutive patients with Covid-19 associated mucormycosis at our tertiary care centre from May 2021 to August 2021. After complete evaluation and clinical investigation, the diagnostic modalities, management options and outcomes were noted. Consent was obtained from all patients, and ethical clearance was acquired from the institutional ethical committee (reference number: F.29(Acad)SPMC/2021/2322). All 123 patients were confirmed cases of Covid-19 associated mucormycosis, and showed broad aseptate fungal hyphae on direct microscopic examination and Mucorales on fungal culture.
Conventional 2D CT of the face was ordered and 3D reconstruction was performed in the same setting. All patients underwent contrast-enhanced MRI for better detection of the extent of soft tissue involvement. The Wipro GE Healthcare (Bengaluru, India) Revolution Evo 128-slice CT scanner was used in this study, with parameters as follows: tube voltage of 140 kVp, tube current of 125 mA, pitch of 0.53 mm/rotation, collimation of 20 mm, field of vision of 25 cm, matrix of 512 × 512, and scan area diameter of 38 × 25 cm which was variable for every patient. Images were acquired in the axial plane with a slice thickness of 0.625 mm, and sagittal and coronal images were reconstructed to 0.54 mm slice thickness. The head was kept in a supine position and a lateral tomogram was obtained. The whole face and skull were continuously scanned. The images were then reconstructed to 3D CT with the help of GE Healthcare AW Server software system (version 16 HW14.9). The CT scan reporting was conducted by senior radiologists from the radiodiagnosis department.
Results
The study included 78 males (63.4 per cent) and 45 females (36.6 per cent), with a mean age of 49.4 years. All patients had a history of Covid-19; 22 patients (17.9 per cent) had active Covid-19 infection at the time of Covid-19 associated mucormycosis diagnosis. A history of diabetes mellitus was present in 54 patients (43.9 per cent). Recent-onset diabetes mellitus was noted in 62 patients (50.4 per cent). The aetiology and risk factor profile were the same in the groups with negative and positive 3D CT findings.
The anterior maxillary wall (Figure 1) was most commonly involved (9.8 per cent). The lateral maxillary wall was involved in 6.5 per cent of patients. The orbital floor, palate and zygomatic process were involved (Figures 2–4) in 6.5 per cent, 4.1 per cent and 4.9 per cent of patients, respectively.
Fig. 1. (a) Coronal and (b) axial two-dimensional, and (c) three-dimensional computed tomography images showing destruction of right anterior maxillary wall, alveolar process and zygomatic process.
Fig. 2. (a) Coronal two-dimensional and (b) three-dimensional computed tomography images showing destruction of left alveolus with no involvement of anterior maxillary wall, which propelled us to perform infrastructural maxillectomy.
Fig. 3. (a) Three-dimensional and (b) coronal two-dimensional computed tomography images showing destruction of right infra-orbital floor, ipsilateral alveolus and zygomatic process.
Fig. 4. (a) Coronal and (b) axial two-dimensional, and (c & d) three-dimensional computed tomography images showing destruction of bilateral anterior and posterior walls of maxilla, with involvement of bilateral alveolus.
Sixty-seven patients underwent endoscopic endonasal debridement, 22 underwent open surgery in the form of total maxillectomy, with 8 undergoing orbital exenteration, and 12 having combined endoscopic and open surgical procedures. Thirty-five endoscopic endonasal debridement patients underwent revision surgical procedures because of disease extension. Twenty-one patients (17.1 per cent) had positive 3D CT findings and hence underwent open surgery in the first instance, avoiding revision surgical procedures. Liposomal amphotericin B treatment was continued in all the patients.
Twenty-two patients (17.9 per cent) did not survive, despite all efforts; this was because of extensive intracranial involvement and other co-morbidities.
Table 1 shows the comparative findings of 3D CT and 2D CT.
Table 1. Comparison of bony involvement detected on 2D and 3D CT scans
2D = two-dimensional; 3D = three-dimensional; CT = computed tomography
As mentioned, the anterior wall of the maxilla was most commonly involved by the disease, followed by the lateral maxillary wall and the orbital floor. Two-dimensional CT and 3D CT both identified erosion of the anterior maxillary wall as being most common. The most common sinus involved was the maxillary sinus (72.3 per cent). Intracranial extension was seen in 17 per cent of patients. Of the patients, 8.1 per cent had orbital involvement.
In 21 patients (17.1 per cent), the decision to perform open surgery in the first instance was made based on 3D CT findings. In these patients, if 3D CT had not been carried out, perhaps we would have planned to perform endoscopic endonasal debridement, a decision which could have changed intra-operatively. Three-dimensional CT reconstruction aided our decision pre-operatively, and multiple or revision surgery was thereby avoided. In 102 patients, 3D CT did not show characteristic findings, and hence we went ahead with endoscopic endonasal debridement. Axial images are precise to the core in locating the anterior, posterior, medial and lateral maxillary walls on CT scans. The coronal scan can detect the involvement of nasomaxillary sutures.Reference Tanrikulu and Erol6
Discussion
Conventional CT depicts anatomy and pathology in two dimensions. The exact depth and extent of disease are difficult to determine from the images. Information gained from a third dimension is valuable for more precise delineation of disease and orientation. The technology capable of demonstrating a third dimension has had a great impact on the pre-surgical planning and adequate management of Covid-19 associated mucormycosis.
The overlying oedema, necrosis and eschar that mask accurate clinical evaluation may make conventional radiography an ineffective tool; in Covid-19 associated mucormycosis cases, such factors might obscure the extent of disease on conventional CT. The facial skeleton has a complex anatomy, with superimposition of various bones, leading to artefacts that result in inappropriate information. The 2D CT images might be difficult to interpret, which could be more time-consuming.Reference Gillespie, Isherwood, Barker and Quayle7 The advantages of 3D CT over 2D CT, even in the presence of oedema and soft tissue involvement, makes it an essential tool for the precise demonstration of the disease process.Reference Frame and Wake8
Our study included 78 males and 45 females. Most studies of Covid-19 associated mucormycosis report a male preponderance, for unknown reasons.Reference Singh, Singh, Joshi and Misra9
In our series, 3D CT evaluation had considerable pre-operative bearing for 21 patients, aiding surgical planning decisions for these patients. We observed that involvement of the anterolateral maxillary wall, along with that of the zygomaticomaxillary region, propelled us to opt for total maxillectomy in 22 patients. It is impossible to eradicate the disease from these sites using endoscopic endonasal debridement. The 3D CT prompted us to change the surgery plan from partial maxillectomy to total maxillectomy. It also provided more accurate information about erosion of the alveolar process; many patients have disease mainly in the alveolar process, without gross sinus involvement. In seven patients, alveolar damage could be identified on 3D CT images (Figure 2), and we subsequently performed infrastructural maxillectomy.
Awareness of orbital floor involvement has a large influence on management. We observed orbital floor involvement (Figure 3) in 18 patients. Peri-orbital involvement was found in 8 patients.
Minimal osteomyelitis or bony erosion can be detected on 3D CT (Figure 5), which might be missed by other investigations or clinical examinations. Three-dimensional CT has proved beneficial in our series; thus, we conclude it to be an important tool for planning the surgical approach.
• Three-dimensional (3D) computed tomography (CT) of the face is superior to conventional CT in determining extent of disease
• Three-dimensional CT is important for pre-operative surgical planning of coronavirus disease 2019 associated mucormycosis cases
• Minor cortical erosions and their finer details are not detected on conventional CT
• Use of 3D CT prevents delays in diagnosis, facilitates surgical planning and reduces need for multiple surgical procedures
• It is a valuable tool in the assessment of revision cases and at follow up
• Post-operative evaluation and follow up are made easier by 3D CT; it is also an important teaching tool and aids patient counselling
Fig. 5. (a) Two-dimensional axial computed tomography (CT) image demonstrates soft issue density over anterior maxilla. (b & c) Three-dimensional CT images showing minor cortical erosion of bilateral anterior walls of maxilla.
Coronavirus disease 2019 associated mucormycosis is a therapeutic challenge for otorhinolaryngologists, not a diagnostic challenge. The disease is fulminant and carries a high risk of mortality, even after treatment.Reference Palejwala, Zangeneh, Goldstein and Lemole10 Until now, we were diagnosing and managing Covid-19 associated mucormycosis based on clinical assessment, 2D CT and contrast-enhanced MRI. The 3D CT technology is a promising diagnostic tool for assessment, and comparison with conventional 2D CT has revealed it as superior in many ways. The advantages of 3D CT over 2D CT are mentioned in Table 2.Reference Ram, Joshi, Debnath and Khanna11 Three-dimensional CT can guide selection of the best therapeutic regimen. Fox et al. concluded that 3D CT can be interpreted more accurately by clinicians.Reference Fox, Vannier, West, Wilson, Baran and Pilgram12 The recent software allows graphic manipulation of volumetric data, and the qualitative information is presented in an easily recognisable pattern for clinicians.Reference Dos Santos, Costa e Silva, Vannier and Cavalcanti13
Table 2. Advantages of 3D CT scans over 2D CT scans
3D = three-dimensional; CT = computed tomography; 2D = two-dimensional
Limitations
The potential artefacts associated with 3D CT, and the inability to represent soft tissue structures or muscles demands additional MRI evaluation. We included confirmed cases of Covid-19 associated mucormycosis and then performed 3D CT; this may not reveal the entire spectrum of disease, as many suspicious lesions remain unconfirmed or the patient may succumb before reaching the healthcare facility. In our study, the size of the sample with positive 3D CT findings was small. Further studies with larger sample sizes will be required for conclusive results.
Conclusion
Three-dimensional CT gives an excellent overview of the gross involvement of disease and degree of destruction of the facial skeleton. As we know, early clinical assessment is important for early diagnosis, and 3D CT performed at the correct time can be crucial, as reconstructed 3D images aptly assist in the clear visualisation of skull bones, bony architecture, fat, muscles and soft tissue windows. Post-operative evaluation and follow up can be enhanced by 3D CT. Three-dimensional CT is an important teaching tool, and aids in counselling patients and their attendants.
Competing interests
None declared
