|Year : 2016 | Volume
| Issue : 4 | Page : 409-415
Multimodal imaging techniques in the diagnosis of metastatic lesions
Abha Rani, Mamatha Gowda Panchaksharappa, Neetha C Mellekatte, Rajeshwari G Annigeri
Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere, Karnataka, India
|Date of Submission||18-Feb-2016|
|Date of Acceptance||03-Dec-2016|
|Date of Web Publication||21-Feb-2017|
Dr. Abha Rani
Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere - 577 004, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Imaging has a crucial role in the treatment of head and neck cancers as it discloses hidden foci of metastases, especially when it is located outside of the planned treatment field. Metastasis to oral cavity is a rare chance and may involve either soft tissue or jaw bones. Their early and accurate detection is critical and also a real challenge for the clinician. Therefore, pre-, per- and post-treatment imaging in diagnosis is critical. Radiography, computerized tomography, magnetic resonance imaging, followed by positron emission tomography, advancements in ultrasonography, and nuclear medicine along with sentinel node lymphoscintigraphy has greatly added to the diagnostic accuracy of metastases.
Keywords: Computed tomography, magnetic resonance imaging, metastasis, positron emission tomography scan
|How to cite this article:|
Rani A, Panchaksharappa MG, Mellekatte NC, Annigeri RG. Multimodal imaging techniques in the diagnosis of metastatic lesions. J Indian Acad Oral Med Radiol 2016;28:409-15
|How to cite this URL:|
Rani A, Panchaksharappa MG, Mellekatte NC, Annigeri RG. Multimodal imaging techniques in the diagnosis of metastatic lesions. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2021 Jan 18];28:409-15. Available from: https://www.jiaomr.in/text.asp?2016/28/4/409/200629
| Introduction|| |
According to Willis, metastases are growths which are separated from the primary growth and have arisen from disseminated transported fragments from it. It is difficult to detect early metastasis because there are no obvious or specific symptoms. Due to aggressive tumor behavior and lack of an effective way to stop malignancy progression, distant metastasis is highly lethal, rapidly leading to patient's death within 3–6 months. Accurate staging of head and neck squamous cell carcinoma (HNSCC) is essential for determining the treatment plan. Treatment plan depends on delineation of the primary tumor, assessment of the presence and extent of lymph node metastases and screening for distant metastases.
| Incidence and Prevalence|| |
Metastases from other body parts constitute approximately 1%–3% of the total oral tumor lesions. These metastases usually affect bone and are less likely to affect the oral soft tissues. The mandible is the most frequent location, particularly the molar region., Metastases are more common in males. Breast and lung are the most common sites from where primary carcinomas metastasize to the jaw bones or oral soft tissue, respectively., Oral metastases are manifested as the first sign of the disease in one-third cases of malignancy. Distant metastasis was reported in 5%–25% of oral SCC patients. In SCC, pulmonary metastases are alone accounting for 66% of distant metastases. Some other metastatic sites include bone (22%), liver (10%), skin, and bone marrow.
| Different Imaging Modalities to Detect Metastasis|| |
Intra- and extra-oral radiography many times helps to determine jaw bone involvement. Radiographic findings of metastases to the jaw do not show pathognomonic radiographic appearance and ranges from minimum manifestation to a lytic or opaque lesion with ill-defined margins. Usually, the osteoblastic and osteoclastic activity determines the characteristic of metastatic bone lesions. Metastases from prostate cancer are usually of osteoblastic nature. On the other hand, bone metastases from kidney, lung, or breast cancers are mostly osteolytic-moth eaten in appearance. Other multiplanar imaging techniques may be needed to determine the degree of spread of some tumors especially, to exclude bone invasion and lymph node involvement such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), as these are more capable of greater spatial and soft tissue resolution than conventional radiography.
A bone scan is acquired by injecting, 550 MBq technetium-99m (99-mTc)-labeled methylene disphosphonate (range 505–820 MBq); approximately 3–4 h later, whole-body scintigraphy/scan with continuous scanning in multiple views is performed using a double-head gamma-camera with a speed of 15 cm/min, low-energy high-resolution collimators, and a 15% energy window over the 140-keV photopeak of 99-mTc. Although bone scan appearances are non-specific, recognizable pattern of bone scan abnormalities suggest a specific diagnosis. Normally liver scanning is not indicated because two-third findings are false negative. Approximately 6% of patients who were diagnosed with cancer of head and neck cancer showed abnormal features in radionuclide scanning of liver.
Advantages of bone scintigraphy are: Detects skeletal physiology, helps in determining the extent of some benign lesions. It is more sensitive as compared to plain radiography. Predicts graft failure in advance before clinical and radiographic changes become evident.
Disadvantages of bone scintigraphy are: Radiation dose is very high, inability to determine exact dimensions of tumor, acts an adjunct to other detecting and determining modalities, and has low specificity.
Computed tomography and magnetic resonance imaging scan
CT is used to evaluate the extent of the primary tumor and metastatic lymph nodes at diagnosis and to detect tumor recurrences and post-treatment complications. It not only helps in metastases characterization but also in tumor staging, tissue sampling and treatment planning. MRI produces excellent quality images with superb contrast, good spatial resolution, and direct multiplanar formats without using ionizing radiation. CT has an advantage of demonstrating bone erosion over the MRI, whereas MRI has an advantage of demonstrating the primary cancer boundaries and its relationship with the surrounding normal anatomical structures over CT. MRI is not preferable in neck region due to artifacts caused by movement made during swallowing, breathing, and coughing.
In short, the major advantages of CT are:
- Rapid acquisition time (2–3 s per se ction)
- Better patient tolerance
- Relatively low cost
- Superior osseous detail compared with MRI
- Superimposition of images of structures outside the area of interest is eliminated
- Tissues differing in density by even <1% can be distinguished.
Disadvantages of CT scan are:
- Soft-tissue contrast resolution is poor
- Risk of allergic reaction due to administration of intravenous contrast material to differentiate vessels from other structures like lymph nodes
- Degraded by scattered artifacts because of metallic dental appliances.
Advantages of MRI are:
- The superior soft tissue resolution of MRI allows high-contrast differentiation between neoplasm and adjacent muscle
- MRI is obtained in multiple planes (sagittal, axial, coronal, and oblique), which is very helpful in assessing tumor mass volumes during and after therapy
- Need for intravascular contrast administration is not required as the patent vessels appear as “signal void,” because of absent signal within their lumen, which helps to easily distinguishes them from surrounding soft tissue structures.
Disadvantages of MRI:
- As MRI sequence are obtained simultaneously rather than sequentially, patient movement during an MRI leads to greater number of artifacts as compared to CT
- Fine-bone detail is inferior to that obtained with CT
- CT has a specificity of 85% and a sensitivity of 82%, whereas MRI has a specificity of 79% and sensitivity of 80%. Curtin et al. (1998) have stated CT is slightly better than MRI, particularly when internal abnormalities were considered in addition to nodal size.
Cone beam computed tomography
From the past few years, cone beam CT (CBCT) has become a popular clinical practice in the three-dimensional (3D) imaging of the oro-maxillofacial region which has made the complex anatomy of maxilla and mandible very simple. It is not only used to rule out the extension of tumors three-dimensionally and related anatomical structures but also helps in postoperative assessment. In comparison to conventional CT it has many advantages such as CBCT has a lower radiation dose, a higher spatial resolution, and same number of or fewer metal-induced artifacts. However, on the contrary, CBCT is not suitable for assessing soft tissue structures., On a CBCT image, infiltration of the jaws can be identified as an irregular osteolysis with loss of cortical structures.
It has been widely accepted that ultrasonography (USG) is superior to palpation in detecting lymph nodes and its metastases. In comparison to other imaging modalities, USG has many advantages such as its low price, low patient burden, and possibilities for follow-up. USG is the method of choice for detecting metastases foci at glandular organs such as the thyroid and salivary glands and in guided biopsy for glandular structures. Compared to CT, USG has comparable spatial resolution and better contrast resolution. Although USG may give a limited field of view, it provides a multiplanar image as in CT and MRI. However, instead of these advantages, many studies have found that borderline lymph nodes cannot be diagnosed with reliability using USG. Hence, USG should not be considered as the diagnostic imaging modality. Furthermore in USG assisted fine needle aspiration cytology (FNAC), there is high chances of aspiration of metastases in the lymph nodes. It has a sensitivity of 72% and specificity of 75% to detect metastases in head and neck.
| Functional Imaging Techniques|| |
These techniques facilitate the assessment of the complex interrelated processes occurring in the cancer tissue microenvironment, such as hypoxia, angiogenesis, metabolism, and pH. These techniques have the potential to (1) predict the cancerous tissue behavior and its response to treatment; (2) to evaluate the effectiveness of anti-cancerous drugs such as the anti-vascular agents; (3) to detect cancerous cells response during treatment; and (4) to identify residual/recurrent cancers.
Positron emission tomography
It is a nuclear medicine imaging technique which uses both different isotopes and different camera system to image the distribution of radioisotopes within the body, but as with conventional nuclear medicine techniques, it is functional imaging method. PET isotopes are radioactive isotopes of atoms normally present in many physiological compounds such as carbon, nitrogen, and oxygen.18F-fluoro-2-deoxy-D-glucose (18FDG) is a radioactively labeled glucose analog with fluorine for hydroxy substitution on a D-glucose substrate. It has a half-life of 110 min that is sufficient to perform a complex process of radiolabelling and reconstruction, and also to keep the radiation dose level low for the patient.
18FDG is utilized due to its unique character to emit positrons, and it can be accurately localized in the scanning process. As tumor cells are very active cells, having an increased uptake of glucose (glycolytic rates), FDG accumulates within tumor cells, producing a “hot spot” on the PET image. These hot spots can easily be distinguished from surrounding normal tissue., PET showed an outstanding performance in detection of unknown primary tumors of head and neck region.,,,,,,,,,, However, along with multiple advantages FDG-PET scan has certain disadvantages also, like high cost, limitation in detecting an occult primary tumor in cervical lymph node metastasis, automatic segmentation of tumor volume is not possible because of increased background signal caused by radiation-induced inflammation. False negatives result in low-grade tumors such as lymphoma and sarcoma. On the other hand, false positive results are seen in inflammatory and infection (abscesses, tuberculosis).
FDG-PET scan has a sensitivity of 90% and specificity of 94%. Thus, PET scan is superior to CT and MRI scan in detecting metastasis (Kitawaga et al., 2003). Nowadays PET scans are used along with CT or MRI scans. This “co-registration or fusion” of PET with CT/MRI gives an advantage to determine both anatomic and metabolic information. It facilitates the exact localization of abnormal minute areas of increased radiotracer activity that would have been a difficult job or rather impossible to localize on PET images alone. PET-CT is also capable to distinguish structures that normally show high metabolic activity from those tissues with abnormally increased activity. Disadvantages of PET-CT are: Patient motion and attenuation (transmission) of artifacts because of metallic objects in the pathway of the CT beam, such as pacemakers, hip prostheses, and dental prostheses. In comparison with PET scan, the fusion scan PET/CT has greater diagnostic accuracy in the patients of head and neck cancer and metastases.
Diffusion-weighted imaging (DWI) is an easy, simple, quick, and functional MR technique, that produces MR images of biological tissues within the body sensitized with the common but specific characteristics based on the difference of the mobility of water in different tissues which lead to generation of DWIs and apparent diffusion coefficient (ADC) maps. ADC acts as a marker of cell density. The ADC value is highest for benign lymphadenopathy and lowest for metastatic nodes. However, the presence of necrosis in metastatic cancers increases the ADC value. DWIs are being used to identify a range of cancers, and the ADC value elucidates the characterization of head and neck tumors and also to monitor the treatment as well as recurrent tumors.,, During treatment, an increase in the ADC value of cancer can result as a result of an increase in cell permeability and swelling, cell destruction, diffusion of water into extracellular space, and necrosis. These changes may also occur in early phases of treatment, preceding volume changes.
Dynamic contrast-enhanced magnetic resonance imaging
Dynamic contrast-enhanced (DCE)-MRI is the acquisition of MRI images before, after and during administration of low-molecular-weight contrast media (1000 Da) intravenously that rapidly diffuse in the extracellular fluid space. The contrast agents used for DCE-MRI are often gadolinium-based. Gadolinium injection lead to decrease in the relaxation time and therefore, images made after contrast media injection have higher signal. First a T1-weighted MRI scan is done without contrast media, then gadolinium is injected (0.05–0.1 mmol/kg) and another T1-weighted scan is made. Then both scans are compared to rule out the difference in blood flow in the tissues. New vascularization or angiogenesis is a signature of neoplasm and is one of the potent principle targets for quantitative imaging.,, It is widely accepted that all solid tumors are dependent upon neovascularization for survival and growth, and many anti-angiogenic drugs are currently in clinical trials. Thus, methods for imaging and quantitatively assessing this angiogenesis will be useful in clinical oncology. In damaged tissues with a lower cell density, the gadolinium stays in the extracellular space longer. In comparison to blood vessel formed by normal physiologic processes, the vessels produced during tumor progression angiogenesis are characteristically ill-integrated, fragile, and incompletely formed., DCE-MRI is an imaging technique that can evaluate the density, integrity, and leakiness of tissue vasculature. However, on the contrary, it has some limitations also like overlapping between malignant and benign inflammatory tissue, failure to reveal micrometastases, and the low predictive value with regard to clinical outcome.
Magnetic resonance spectroscopy
Magnetic resonance spectroscopy (MRS) helps in characterization of tissue, forming their anatomic images by interrogating the concentration of certain metabolites during usual cell metabolism with the help of same conventional MRI machine. The most commonly used nuclei in MRS are 1H (proton), 23Na (sodium), 31P (phosphorus). Because of better results due to high signal-to-noise ratio, proton spectroscopy is more preferred as compared to other nuclei., Spectroscopy is a test series that measures the chemical metabolism taking place in different tumor types. There are many metabolites/products of metabolism that can be used to differentiate between tumor types. While MRI identifies the anatomical location of a tumor, MR spectroscopy compares the internal biological reactions in cases of stroke, epilepsy, metabolic disorders, infections, and neurodegenerative diseases and differentiates with that of normal surrounding tissue. The biochemicals which can be detected in MRS include choline-containing compounds (cell membranes), creatine (energy metabolism), inositol and glucose (sugars), N-acetylaspartate, alanine and lactate which are elevated in some tumors. By comparing the frequencies of metabolites in normal and tumor tissue, the type of tissue can be identified and distinguished. Lactate is also been found as a potential biomarker in detection of metastatic nodes from HNSCC.
Blood oxygen level-dependent magnetic resonance imaging
Blood oxygen level-dependent (BOLD) is a non-invasive functional MRI modality that can identify hypoxic cancers (deoxy-hemoglobin) which are likely to respond to radiotherapy and chemotherapy. The BOLD technique takes advantage of the fact that the change from diamagnetic oxyhemoglobin to paramagnetic deoxyhemoglobin, that takes place with tumor mass activation, results in decreased signal intensity on MRI. Abnormal tissue mass are detected on the basis of their differential magnetic susceptibility. There are several limitations for BOLD technique: Signals produced by BOLD may not be result of oxygenation only, short-lived effect of hypoxic tissue which lead to nonreproducibilty of results, and several times changes in signal are minute to detect. But, in spite of certain limitations, BOLD has been proved to be successful to detect decrease in blood deoxyhemoglobin in human cancers ,, and thus joins a helping hand in treatment for hypoxic cancers.
| Strategic Planning in Detection of Metastasis|| |
Strategic planning for lymph node metastases detection
Cervical lymph node metastasis is one of the most important prognostic factors in treatment of HNSCC. A meta-analysis concluded that, for the detection of lymph node metastases, US and especially US-guided FNAC, CT, MRI are the techniques with better diagnostic value than that of conventional imaging. FDG-PET has also an excellent diagnostic role in the overall evaluation of the presence of lymph node metastases in HNSCC patients. The most important indicator in HNSSC prognosis is detection of occult lymph node, particularly micrometastases (>0.2 mm but <2.0 mm). A meta-analysis by Kyzas et. al., inferred that, only 50% of the occult lymph node metastases can be detected by FDG-PET. This led to the use of sentinel lymph node scintigraphy, which proved to be a valid alternative to elective stage dissection. FDG-PET with CT/MRI has been found to be more accurate than FDG-PET alone in detection of subclinical lymph node (N0) metastases. Thus, PET and PET-CT have the highest accuracy for detecting occult micrometastases in cervical lymph nodes.
New high-resolution MRI like DW-MRI is also considered complimentary to standard MRI. Further implementation of DW-MRI into routine imaging will mostly depend on the standardization of imaging technique and interpretation.
Strategic planning for detection of distant metastases
The incidence of distant metastasis in HNSCC is directly related to the stage of disease. Till date, no comparisons between the accuracy of CT, PET, PET-CT were not made. Chest CT is a gold standard for detection of lung metastasis (most common) from HNSCC. Introduction of multi-receiver channel MR has brought a miraculous change in imaging world, now whole-body MRI has become possible, which has potential to detect metastases of primary head and neck tumors.
Most studies that used FDG-PET for screening of distant metastases are deficient in valid comparison between PET and CT. With high spatial resolution, multi-detector row CT may act as an imaging tool comparable to FDG-PET in evaluation of distant metastases in HNSCC patients and help to rule out FDG abnormalities. Combination of PET and CT in PET-CT provides the most attractive, most accurate and onestop option. Besides advancements, in clinical practice the detection of distant metastases during follow-up is of minimal concern since currently no treatment options with complete cure is available.
| Conclusion|| |
The diagnosis of metastatic lesions is a real challenge, to both the clinician and the radiologist. Tumor thickness is more critical than the size of the tumor in terms of prognosis, and it is closely related to metastasis. The tumor primary site, tumor thickness and degree of differentiation are the most important determinants for metastasis. Early detection of metastasis is the most efficient way to reduce the high mortality and morbidity resulting from it. Pretherapeutic imaging has predictive value for patient outcome. Based on per-therapeutic imaging, personalized replanning during radiotherapy may help to increase control rates and reduce toxic effects to normal tissues. Post-therapeutic imaging is of utmost importance in detection of recurrent tumors. Hence, it is an urgent need to devise efficient diagnostic tools for early detection of oral dysplasia, malignancy and metastasis that are diagnostic, noninvasive and can be easily performed in an outpatient set-up.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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