Non-enhanced, arterial, and venous-phase (left to right) axial CT images from a 4DCT in a patient with primary hyperparathyroidism shows an ovoid parathyroid adenoma posterior to the right tracheoesophageal groove that measures lower density that thyroid parenchyma on the non-enhanced scan (50 Hounsfield units [HU]), avid enhancement on arterial phase (middle-122 HU), and subsequent contrast washout with venous-phase density of 84 HU
The applicability of 4DCT for detection and localization of parathyroid disease is based on multiple factors including (1) the differential attenuation of parathyroid tissue and thyroid parenchyma on pre-contrast imaging, (2) the differential contrast enhancement and washout of parathyroid lesions versus adenoma mimics such as lymph nodes, (3) improved spatial resolution of CT relative to scintigraphy, (4) improved visualization of deep and ectopic lesions relative to ultrasound, and (5) superior visualization and spatial discrimination of structures within and adjacent to the planned surgical approach such as blood vessels.
On non-enhanced imaging, parathyroid adenomas are characteristically less dense than iodine-rich thyroid parenchyma, a feature that can be helpful in distinguishing orthotopic parathyroid lesions from exophytic thyroid nodules. Secondly, most parathyroid adenomas, over 92 % in one study, show hyper-enhancement on (near-equivalent enhancement to nearby arteries) arterial phase CT imaging . Delayed or venous-phase imaging characteristically reveals a decrease in the density of parathyroid lesions relative to the arterial phase acquisition. Such a pattern allows differentiation of parathyroid lesions from lymph nodes, which characteristically display a gradual accrual of contrast and thus show a stepwise increase in attenuation from pre-contrast to arterial and delayed venous-phase imaging (Fig. 14.2).
Graph of measured density (y-axis) over time (x-axis) for parathyroid tissue (blue) and a cervical lymph node (green) demonstrates the differential enhancement kinetics displayed by these tissues, with parathyroid showing early peak and subsequent washout and lymph nodes displaying continued accumulation of contrast throughout the scan
Variability of the enhancement characteristics of parathyroid lesions (including both adenomas and hyperplastic glands) prompted Bahl et al. to develop a categorization scheme based on attenuation of a candidate lesion relative to the thyroid parenchyma. Type A lesions are higher in attenuation than the thyroid in the arterial phase (20 % of parathyroid lesions); type B lesions are not higher in attenuation than thyroid in the arterial phase but lower on the delayed phase (57 % of lesions); type C lesions are neither higher in attenuation than thyroid in the arterial phase nor lower in the delayed phase (22 %) . Such differences in the enhancement characteristics demonstrate the value of a multi-phase examination including at least three phases. In particular, for type C lesions which are not distinguishable from thyroid parenchyma on either the arterial or delayed-phase acquisitions, a pre-contrast examination serves as the only reliable mean by which to verify that a candidate lesion is indeed of parathyroid origin.
Practice patterns of individual surgeons and at different institutions regarding the choice of localization modality vary widely; however sestamibi-based imaging (MIBI) and ultrasound remain the most widely used techniques. Many surgeons rely on congruent localization by two different modalities prior to MIP. The role of CT in the preoperative imaging scheme is not fully established due to its relatively recent introduction; however, CT has gained a foothold at several institutions and a complementary localization technique, particularly for patients with negative US and/or MIBI exams. Given the now established superiority of CT to US and MIBI imaging in terms of sensitivity and positive predictive value for adenoma localization (discussed in “Test Characteristic” section) the use of CT may continue to expand in the coming years.
Comparing CT to other well-established parathyroid imaging modalities, US has several benefits including the ease of performing “in-office” exams and lack of any ionizing radiation. Ultrasound is a heavily operator-dependent modality that therefore performs optimally in the hands of an experienced, sub-specialized operator and relatively poorly when conducted by an operator with less experience or by an individual who is unfamiliar with US imaging of the parathyroid glands. Further, US is limited in its ability to detect lesions in ectopic or posterior orthotopic locations due to limited depth of penetration and obscuration of tissues deep to air-filled structures such as the esophagus and trachea. Limitations of MIBI include the nonspecific nature of sestamibi, which is taken up my mitochondria-rich cells regardless of whether or not these cells are located within a parathyroid lesion. As such, the degree of radiotracer uptake correlates with the size and cytological composition of parathyroid lesions, with some lesions being either too small or oxyphil-poor to be detectable by MIBI . Lower sensitivity of US and MIBI has also been encountered in patients with only mildly elevated PTH and calcium and in obese patients . Lesion size and volume have been shown to be strong independent predictors of successful localization of parathyroid adenomas by both US and MIBI, with decreased ability of these exams to localize smaller lesions (<500 mg) [10, 9]. Not only has 4DCT proven to be efficacious for localization of small parathyroid adenomas, but also allows imaging visualization of normal, non-adenomatous parathyroid glands measuring (typically measuring between 1 and 3 mm in long-axis diameter) in some patients (Fig. 14.3).
An axial arterial phase 4DCT image demonstrates a left-sided retroesophageal parathyroid adenoma (dashed arrow) plus an additional enhancing lesion at the eutopic left superior position thought to represent a normal parathyroid gland
Radiation dose of 4DCT is among the chief concerns limiting adoption of the technique. Since the initial description of 4DCT in 2006, many institutions have developed low-dose 4DCT techniques through adjustment of scan parameters and reduction in the number of acquisitions making up the scan. Calculated effective radiation doses for 4DCT have been reported to range from 10.4 (Mahajan 2012) to 28.5 mSv (Hoang 2015) compared to 7.8–12.0 mSv for single-phase planar sestamibi scintigraphy and SPECT [9, 11]. To put these numbers in perspective, the estimated annual background radiation exposure in the US is approximately 3 mSv and the annual average per-capita US radiation dose received from medical procedures is 3.2 mSv (Mahajan 2012). Hoang et al. further explored radiation exposure related to 4DCT by examining organ-specific dose and found that thyroid, salivary glands, and esophagus received the highest dose, whereas with scintigraphy the colon is exposed to the highest radiation dose of any organ in the body. Considering a lifetime incidence of cancer of 46,300 cancers/100,000 population, imaging increases the lifetime incidence of any cancer above baseline by 0.52 % for 4DCT and 0.19 % for scintigraphy. Lung cancer had the highest lifetime attributable risk in both the 4DCT and scintigraphy groups at 98 cancers/100,000 in the 4DCT cohort and 51 for scintigraphy. Lifetime attributable risk for thyroid cancer for 4DCT patients 55 years of age or older was only 3 cancers/100,000 patients despite the relatively high organ-specific dose (Hoang 2015). The higher estimated attributable risk for thyroid cancer in younger patients, 92 cancers/100,00 for female patients at age 25, and 23/100,000 for 25-year-old males warrants consideration of patient age when decided which imaging modality is most appropriate. Any discussion of relative radiation dose between 4DCT and MIBI must also take into consideration the improved sensitivity of the CT technique which translates into fewer initial negative studies and therefore negates the need for additional workup.
4DCT for parathyroid disease entails acquisition of imaging data at different time points in order to add physiologic data on top of anatomic and differential tissue contrast data provided by a single-phase CT exam. Techniques for 4DCT vary somewhat from institution, but the most widely utilized protocols today use a pre-contrast study followed by early and delayed contrast-enhanced exams. Such three-phase studies represent a modification of the earlier employed 4DCT technique using a pre-contrast scan followed by three post-contrast scans. This change came about as a response to concerns over radiation dose and the advent of data showing no clear diagnostic benefit of three post-contrast phases. Timing of the post-contrast acquisitions varies, but most institutions using 4DCT have reported a 25-s or 30-s delay from the beginning of contrast administration to the initiation of the first post-contrast scan followed by an additional scan at 80–90 s. Commonly reported contrast agents for 4DCT include 75–100 ml iopamidol (Isovue-300; Bracco, Princeton, NJ) or iohexol (Omnipaque 350, GE Healthcare) injected via a 20-G cannula in a right antecubital vein at a rate of 3–4 mL/s followed by a saline chaser. At our institution we use 75 ml iohexol 350 injected at a rate of 4 ml/s followed by 40 ml saline. In 2015 Lawson et al. published a video manuscript discussing the 4DCT technique employed at the University of Arkansas for Medical Sciences .
Anatomic coverage for multi-phase parathyroid is typically smaller than that of neck CT examinations performed for other indications, the vast majority of which require a single-acquisition phase, in order to minimize the radiation dose to the patient. Cephalad coverage typically begins at the angle of the mandible and extends through the aorticopulmonary window or carina. Some centers further constrain the area of coverage on the pre-contrast phase from the hyoid bone to the clavicular head based with the primary utility of this phase being for differentiation of orthotopic parathyroid lesions from thyroid nodules. Additional scan parameters include field of view 180 mm, 120 kV (peak), and automatic tube current modulation with maximum of between 400 and 700 mA. Many centers set a higher threshold mA for the arterial phase acquisition (700 mA) and a lower maximum threshold of 400 or 500 mA for the pre-contrast and delayed phases as a further means to reduce patient radiation exposure. Detector configuration will vary according to each institution’s available hardware. At our center we use a 64 × 0.625 mm configuration. Contiguous axial images of each phase reconstructed at 1 mm are sent to the picture archiving and communication system (PACS) for interpretation and are available for customized multi-planar reconstructions as required for problem solving (Fig. 14.4). Axial, sagittal, and coronal 2 0 mm thick reconstructions of each phase are also made available on PACS.