Imaging studies

Bone disease is a common symptom of multiple myeloma: 70%–80% of patients are found to have bone disease at diagnosis. Imaging studies that assess the status of a patient's bones and/or bone marrow at diagnosis and relapse are:

• X-rays 
• CT or CAT scans
• MRI studies
• PET scans
• PET/CT scans

You can learn more about each of these imaging studies below:

X-rays

X-rays of the whole body were the standard of care for diagnosing and assessing myeloma-related bone damage for many years. More sensitive studies are now recommended due to the limitations of X-rays.

The limitations of X-rays include the following:

• 30% or more of the trabecular bone (the spongy part of the bone containing fat and bone marrow, where myeloma cells grow) must be missing before an X-ray can reveal the damage. A study showed that bone loss in lumbar vertebrae can be seen on an X-ray only when 50%–75% of the trabecular bone has already been destroyed.
• X-rays are not a sensitive study for focal lesions in the bone marrow.
• The appearance of a lytic lesion on an X-ray does not change following therapy, even if there is no longer any active myeloma there.
• X-ray provides low visualization of the spine and pelvis.
• X-ray cannot accurately depict the cause of lesions in myeloma.
• Because whole-body X-ray (WBXR) requires 20 separate films, the study is time-consuming.

MRI (Magnetic Resonance Imaging)

Magnetic resonance imaging (MRI) is a non-invasive study that uses magnetic energy and radio waves, not radiation, to produce a detailed two- or three-dimensional image of structures inside the body. MRI scans map the location of water and fat in the body and produce detailed spatial images.

Why are MRIs useful for diagnosing and monitoring multiple myeloma?

MRIs can image early focal lesions in the bone marrow. Because an MRI creates images of soft tissue, it can show small clumps of myeloma in the bone marrow, plasmacytomas, and compression of the spinal cord by these masses.

The best setting for MRI is early in diagnosis. MRI is highly sensitive for the detection of focal lesions before bone destruction occurs. In a large comparative study of X-ray and MRI, 52% of patients had normal-appearing whole-body X-rays, but they had focal lesions that were apparent on MRIs. The IMWG guidelines on MRI state that because MRI is a more sensitive study than X-ray for focal lesions (before the appearance of lytic bone lesions), all smoldering multiple myeloma patients should undergo

• whole-body MRI (WBMRI) or
• spine and pelvic MRI if WBMRI is unavailable.

The limitations of MRIs

• MRI is an expensive, time-consuming procedure.
• Patients who have metal implants cannot undergo MRI.
• Claustrophobic patients can't undergo an MRI.
• There is approximately a 9-month or longer lag time before an MRI will look normal after an area of myeloma has been successfully treated and is no longer active, leading to a high false-positive rate. The IMWG guidelines therefore state that the use of MRI “for the follow-up of patients, before or after different therapies, in the absence of clinical indications is not recommended.”
• Treatment for myeloma will interfere with MRI results. If possible, myeloma patients should not start treatment before a scheduled MRI.
• The MRI scanning technique that is best for myeloma (with diffusion-weighted imaging) has not been standardized and is not widely available

The use of the contrast agent gadolinium in MRIs 

Gadolinium contrast is a particular problem for myeloma patients with kidney involvement. It should be possible to perform an MRI without gadolinium contrast to assess myeloma bone disease. 

• The contrast medium gadolinium used to enhance the MRI image may be contraindicated in myeloma patients, many of whom have some level of kidney damage. In addition, in late 2017 the FDA set up an investigative committee to evaluate “recent findings of gadolinium retention in the brain and other organs,” to determine “how to minimize potential risks moving forward.” The committee has not yet issued the investigation and report. Contrast is not usually required for MRI scans of the bone. Discuss the use of gadolinium contrast with your doctor before they write the order for your scan. See the FDA's overview of gadolinium contrast risks. 

CT or CAT Scan (Computerized Axial Tomography)

Computed tomography (CT) scan, sometimes called computed axial tomography (CAT) scan, is a radiological study that uses X-ray technology to create a cross-sectional, three-dimensional image of the inside of the body. It is a more precise study than X-ray and can provide clear, detailed images of bone.

• CT allows for the detection of small bone lesions that are not detectable by plain X-rays.
• In 20%–25% of patients with negative X-ray studies, whole-body CT will detect destructive bone lesions.
• CT can detect soft tissue masses that are not visible on X-ray.
• CT provides a more comprehensive assessment of fracture risk and the stability of collapsed vertebrae than X-ray.

How are whole-body low-dose CTs (WBLDCTs) used in myeloma patients?

Dedicated low-dose (of radiation) whole-body CT protocols have been developed for imaging the bones of the skeleton. Whole-body low-dose CT (WBLDCT) is now recommended by the IMWG as the standard of care to detect and document early bone disease. It is the preferred baseline imaging study for newly diagnosed myeloma patients.

The advantages of whole-body low-dose CT scans in myeloma:

• WBLDCT is faster and more convenient than whole-body X-rays.

• WBLDCT uses two to three times less radiation than conventional CT.

• WBLDCT does not require the use of contrast agents.

In 2017, the IMWG published a study, concluding that whole-body CT, either alone or as part of a PET-CT protocol, should be considered the current standard for the detection of osteolytic lesions in myeloma. Then, In 2018, the IMWG published its recommendations for acquisition, interpretation, and reporting of WBLDCT in patients with myeloma and other plasma cell disorders, thus establishing international protocol standards for this imaging study that can be followed by radiologists everywhere. By 2019, the IMWG published guidelines on optimal use of imaging methods at different disease stages.

The limitations of CT scans:

Like MRI, CT cannot be used for treatment monitoring because bone lesions in myeloma regress slowly or not at all, even in patients in complete remission.

• CT is not as sensitive as MRI in detecting lesions outside the bone marrow (extramedullary disease) or in the vertebrae and pelvis.
• CT is an expensive study.
• Even in low-dose format, CT uses an increased level of radiation as compared to X-ray or to MRI, which doesn’t use radiation at all.

PET or PET-CT Scans

Positron emission tomography (PET) scanning is a “real-time” study that shows where, and to what extent, cancer cells are actively dividing in the body.

Before a PET scan, a patient is injected with a sugar-fluorine compound (FDG, or fluorodeoxyglucose). This compound is taken up by the body’s actively multiplying cells as fuel for cell division. When the body is scanned, the areas with the highest concentration of sugar-fluorine uptake glow. The glow is caused from positrons emitted by the fluorine. This process reveals “hot spots” where rapid metabolism can indicate areas of active cancer cell division. This scan covers the whole body. It is very sensitive in detecting potential tumor activity. It is measured in units of Standardized Uptake Value (SUV).

The advantages of PET scans

PET scans can:

• Assess metabolic response to therapy. PET-CT is the preferred imaging study in this setting.
• Assess the status of patients with non-secretory myeloma, whose disease cannot be monitored with standard blood and urine tests.
• Detect lytic bone lesions at diagnosis as a baseline test before therapy.
• Predict progression-free survival (PFS) and overall survival (OS). Three or more PET-positive lesions are an independent predictor of poorer PFS and OS.

The advantages of PET-CT Scans

• Highly accurate and a valuable imaging technique used in diagnosis, therapy assessment, and prognosis of myeloma.
• Combines PET scan with CT in areas where there is high uptake of FDG.
• Provides information about past damage and current myeloma activity, thus enabling the doctor to study changes over time.
• Its sensitivity and ability to detect disease in areas outside the bone marrow has allowed PET-CT to be included along with specialized testing of the bone marrow biopsy specimen to establish MRD-negative status following treatment.

The disadvantages of PET scans

• They are time-consuming and expensive.
• Because areas of infection and inflammation can also take up FDG, PET scans can produce false-positive readings for cancer.
• There is some concern that skull lesions could be missed because of the normally high FDG uptake in the brain.
• As with MRI, therapy can interfere with PET results. Patients should not start therapy before a scheduled PET scan. Dexamethasone in particular is problematic. Dexamethasone interferes with PET results by slowing down the entry of glucose into tumor cells. PET studies used to determine the effect of treatment should not be performed until after the patient has been off dexamethasone for 2–3 weeks, and before the patient starts the next cycle of dexamethasone.

In the U.S., the Centers for Medicare and Medicaid Services (CMS) currently covers the cost of one FDG PET scans.The CMS allows private health insurers who function as local Medicare contractors to decide whether or not to cover further PET scans, depending on each patient’s particular medical problem.

Doctors who wish to support the need for additional PET scans can do so based on the following justifications:

• Disease recurrence
• Non-secretory disease
• Concern about infection or a second primary malignancy (SPM)

Bone Density Testing

Bone density testing is useful for monitoring the effects of bisphosphonate therapy on the bones of patients who have diffuse thinning (osteopenia or the more severe condition, osteoporosis) of the outer bone cortex. It is not a useful test in assessing myeloma bone disease.

Another bone-related test that is not useful in myeloma is the nuclear bone scan. Myeloma causes bone loss resulting in lytic lesions, which do not show up on a nuclear bone scan.

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