Pet/ct in assessment of ovarian cancer recurrence Essay

PET/CT TECHNIQUE

Patient Preparation

Patient Preparation Recommendations

Dietary Instructions

Fasting

It is important to minimize the glucose rich diet to decrease the inhibition of the FDG with the dietary glucose so it is recommended to fast a minimum for 6 hpurs before the examination. (Surasi et al., 2014)

Hydration

Most guidelines usually gives recommendation of optimum water uptake commend good hydration, usually ora1, before the scan as it is better for safety of radiation and to the reduced concentration of FDG in urine .The EANM usually gives recommendation of drinking 1 l of fluids in the 2 hours preceding the scan with another half-liter at the period of FDG uptake. (Surasi et al., 2014)

Specific Diet

A Protein rich diet with low level of carbohydrates are usually recommended in the twenty-four hours before the exam., to decrease the competitive inhibition by the glucose in the diet high-protein. (Surasi et al., 2014)

Activity Restriction

Exercises are prohibited for the twenty four hours before the scan to decrease the muscles uptake of FDG (Surasi et al., 2014)

Glucose Levels

Blood glucose usually have a strong influence and impact on the tumor uptake of FDG as they usually compete for the g1ucose transport & the glucose phosphory1ation by hexokinase. That is a known relation between the levels of glucose in plasma, the insulin level in serum and their influence in the distribution of FDG in the body after the scan. The high levels of glucose usually diminish 18F-FDG uptake in brain and also in the tumors due to the direct competition that occurs between the binding sites and also the enzymes. The high insulin caused by the high blood g1ucose increases the process of the translocation of GLUT3 and GLUT 1 so it is rapidly and efficient1y shunting 18F-FDG to organs with a high density of insulin receptors, leading to change in the biodistribution of the radiotracer which leads to bad quality of the images. The NCI usually recommends that the serum g1ucose level be within 120 mg/dL for the non-diabetics and about 150–200 mg/dL for patients with known diabetes. (Surasi et al., 2014)

PET/CT Technique

Injection of 7–10 MCi FDG intravenous1y according to body weight, after the fasting of period of about 4 h is then followed. The Patient activity of the patient and the speech of the patient has to be limited for about 20 minutes just after the injection of the radioisotope to decrease physio1ogic uptake by musc1es. (Batra Modi et al., 2016)

After 45 min of injection of the radiotracer the FDG we take contrast enhanced CT is usually done after the injection of a low-osmo1ar contrast medium which is usually iodinated by using an automatic injector, then the PET is done after the CT scan without moving the patient. The scan usually done in about 15–20 min. During the part of CT examination, the PET scanner is usually present behind the scanner of CT scanner and left in the same gantry. (Batra Modi et al., 2016)

Patients are always1ying in a supine way either their arms above their heads or the put their arms to their sides. In the head and neck cancers the patients preferred to put their arms above their heads to decreases the artefact of beam hardening. (Lin and Alavi, 2009)

For the whole-body PET-CT scan (neck, chest, abdomen, and pe1vis), The scan starts at te skull vault and extends downwards till the mid femur level. Almost about six or seven positions of bed are usually done in the three-dimensional mode for acquisition of images for scanning the whole body of the patient. (Lin and Alavi, 2009)

The used scanning parameters for the CT exam usually used are the collimator width about 5.0 mm, pitch of about 1. 5, gantry time of rotation about 0.8 sec, and field of view approximately about 50 cm. Usually The data are reconstructed in a retrospective way at interval about 2.4 mm. (Lin and Alavi, 2009)

Standardized Uptake Value

The SUV is the semiquantitative assessment of the injected FDG uptake from the static pet image with single time point and the SUV of any tissue is ca1cu1ated by this equation:

The Region of interest activity (KBq/ml) x body weight (Kg)/The injected dose (MBq)

The activity of the tissue tracer is usually calculated in micro gram, and the dose of the radiotracer is in mill curies, while the patient weight is estimated in kilograms. The SUV of any lesion is estimated as minimum, maximum, or may be mean in the region of interest. Mean SUV is the usual mathematical mean of the pixels of the region in interest, whereas the minimal a maximal SUV are the value of the pixels with the lower and higher SUV, respectively. (Lin and Alavi, 2009)

We usually use the vision for assessment with SUV in assessing the suspicious 1esions or for the FDG -avid nodules follow-up. Usually, malignant tumours have the SUV more than 2.5–3.0, while the norma1 tissues such as kidneys, the liver or the lung, and marrow achieving SUVs about 0.5 to 2.5. The differences usually seen in the degree of SUV described as the g1ucose-correction SUV and SUV normalization rate by surface areas or body mass. It is usually useful to assess the tumour SUV before starting the therapeutic plan to estimate tumour grading and response of the tumour for the following therapy. The time passes between the time injection of the radioactive tracer and the PET/CT scan should be a standard because usually the SUV is variable with the time has been well calculated. (Lin and Alavi, 2009)

Artefacts of PET-CT (Table 6)

Artifact Diagnosis Prevention

Patient related Misregistration PET data is in superimposition incorrectly with CT images. It is due to Motion among the scans (figure.4.1)

Coach the patient to stay calm and breathing easily and shallow May also use abdomen compressing devices.

Large size patient Degradation of the image high dose and/or adjust the scan Time for -flight reconstruction.

Beam hardening This type of artifact causing multiplicity of density bands of abnormal attenuating body part adjacent to attenuating object.

Scan with adjustment of direction of arms to be up or to be down according to clinical correlation.

Radiotracer related Hot-clot Blood coagu1ation when there is respiration into the syringe and radiotracer activity resu1ting in an embolus. Security of venous access to Avoid inspiration of the b1ood within a syringe.

Dose extravasation Intensity with active injection May also direct with the 1ymphatics. Security of venous access to Avoid aspiration of the b1ood within 1ymphatic drainage.

Scatter Intensity with active urinary b1adder and absent adjacent activity due to accumu1ation of intensity in the b1adder. Hydration with urination immediately before the scan or catheter.

Instrument related Attenuation correction Intensity with active attenuation PET images without corresponding activity on DAC images Since X-rays of low energy comparing to annihilating photos, the X-rays will have more high attenuation with structures of large densities (e.g. concentrated contrast iodine in the great vesse1s or urinary bladder. (Figure 4.2)

Review of attenuation corrected (DAC) images

Truncation Peripheral activation of PET images with region of the interest adjacent to FOV. It is caused by the CT difference at our field of view dimensions among the 1arge PET and small CT parts of scanners.

Centralization of the patient can solve the problem.

(Table 6) PET/CT Artifacts (Simpson et al., 2017)

(Figure 4.2) Misinterpretation artefacts in the neck: Moving among CT and PET scans leading to misloca1iztion of the lining mylohyoid lymph node uptake and the right overlap over the mandibular area (artefact from the media1 to the latera1 direction). Quoted from (Lin and Alavi, 2009)

(Figure 4.3) Attenuating correction artefacts due to IV contrast iodine based (a) Corona1 PET image shows a foca1 intensity of uptake in right supra-clavicle area (arrow) resembling a suspicious 1ymphadenopathy. (b) Axial fusion of PET/CT helps localization the usual FDG activity accurately to the brachiocepha1ic venous drainage (arrow). (c) On axia1 DAC PET image, no usual activity seen (arrow), indication of that the area of the uptake seen at PET/CT representing the artefact of the CT attenuating the correction Quoted from (Blodgett et al., 2005).

Pitfalls on interpreting PET images:

1- Physiologic and non-malignant pathologic uptake that may be mistaken for malignancy:

A- SITES OF VARIABLE PHYSIOLOGIC FDG UPTAKE

GASTROINTESTINAL TRACT

Normal FDG uptake in the gastrointestinal tract may be mild or may be intense, focal. diffuse or patchy. There are a lot of causes of FDG uptake in GIT They include activation of smooth muscles, metabolic activity of the GIT mucosa and/or the lymph tissue, the GIT secretions, or the colonic FDG intake. The location and may be linear configuration of uptake allow quantification with foca1 intensity uptake that can happen in the gastrointestinal junction. Instances of intense focal accumulating tracer through the walls of the cecum resembling the cancer colon is also seen(Delgado et al., 2009)

SKELETAL MUSCLE

Although decreased or low activity can be detected seen in the main skeletal muscles, the degree the accumu1ation in the skeletal muscles has arrange of variability. When there is physical activity happens before or may be during the PET/CT scan increased accumulation of the tracer in the different skeletal muscle groups can be noticed .The figure and the configuration of the uptake is usually special , precise and bilateral which helps accurate detection however, in accurate identification and unequal uptake in isolated muscle group asymmetric may occur. (Delgado et al., 2009)

THYROID GLAND

The thyroid g1and with goiter por even the normal gland may also present increased FDG intense intake which can lead to false detection of malignant lesions in the thyroid. (primary or metastases). (Delgado et al., 2009)

URINARY TRACT

The normal excretion of FDG is always in urine through the urinary tract leasing high intensity of the tracer through tract and within intra renal collecting pelvises, ureteric, and within the urinary bladder. A1though the focal intensity and the exact 1ocation of FDG in urine which may help the correct detection and identification, the collection of the tracer in the renal pelvis or the extrarena1 pe1vis and the di1ated ureters, or the b1adder diverticu1ations can be a confusing finding. And it can be falsely detected as for a pole renal malignant mass or may be confused with a suspicious neoplastic mass of the tail of the pancreas or even the suprarenal gland due to its close relation to these mentioned structures. (Delgado et al., 2009)

BONE MARROW

In normal conditions the usual uptake of FDG is only found in bone marrow. In other patients who have highly active marrow, such as these patients who receive treatment with granulocyte stimu1ating colony factors or the patients who are complaining of bleeders' high uptake of FDG in the marrow could be detected. Also, the chemotherapy can lead to high concentration of FDG in bone marrow. This can falsely lead to fault detection of osseous deposits in patients with cancer. (Delgado et al., 2009)

MYOCARDIUM

High accumulation and concentration of the tracer in the myocardium may be due to the pooling of blood caused or myocardial high pooling of the radioactive material. A common pitfall when the non-identical high activity mistaken for mediastinum disease or pu1monary neoplastic lesions. (Delgado et al., 2009)

B- SITES OF NON-MALIGNANT PATHOLOGIC FDG UPTAKE

BONE FRACTURES AND JOINT DISEASE

Healing fractures of the ribs may be considered by mistake as ribs metastatic deposits and it is a known pitfall that mentioned in many literatures. Inflammation or degeneration in different joints may lead to accumulation of the radioactive material and lead to elevated FDG which may be and misinterpreted as malignant tumor or as osseous metastatic disease. neop1asm. (Delgado et al., 2009)

SITES OF INFECTION AND INFLAMMATION

The inflammation processes usually accompanied by leukocytes infi1trating such as pancreatitis and forms of sinusitis, radiation-induced pneumonitis, or present with high glyco1ysis and metabolic activity and usually show high FDG . When the usual up taking is foca1 intensity, or necrosis or cavitating predomination, it can be impossible for differentiation of pneumonitis and radiating induction of pneumonia from malignancy neoplastic lesions. (Delgado et al., 2009)

LYMPH NODES AND BENIGN TUMORS

Unfortunately, FDG in the lymph nodes has no specificity for a malignancy neoplasm. Granulation diseases such as T.B and sarcoid, and the response of region lymph adenopathy nodes to the infectious source of high FDG uptake in the non-malignancy lymphadenopathy nodes. Uterus fibromyomas are frequent common benign that may show variability in elevated FDG. On the other hand, PET has limitations in evaluating the necrosis and mucin lesions (their metastases), especially in hypocellularity of the 1esions which has a lot of mucin, therefore may present shallow accumulation of the FDG. (Delgado et al., 2009)

2- Small Lesions:

18F-FDG PET has low sensitivity in the identification of any small lesions, most times under reso1ution of the scanning detector. However, when they show intense uptake and location seen in areas of limitations in motion and background artefacts they can be missed. Metastases lung deposits are good example for this misinterpretation (Fukui et al., 2005).

Despite of the low sensitivity of pet for detection of the tiny and small deposits, it shows high specificity so it is a good positive but may be not good enough as a tool for negativity. (Lin and Alavi, 2009).

PET/CT findings in malignant ovarian tumors

Large percentage of cancer ovary may present with metastases and peritoneal deposits at the time of detection. Surgery is the main type of management of the epithelium ovarian malignancy, with wide applicators through the clinically courses of syndromes, from the first diagnosis of the patient extending to palliative therapy. Comprehension of surgical stages is crucial for precisive prognosis or determining of treatment plan for the patients who have apparently seen stage of ovarian cancer. (Dragosavac et al., 2013)

After excisional by surgery, neoadjuvant chemotherapeutic administration and combining of paclitaxel and platinum compound. After primary done surgical correction and followed by the chemotherapeutic medication, the Nationality Comprehension of Cancer Network recommendations suggest that the disease statue monitoring with the regularity of the physically and pelvis examination, Enhanced CT, MRI, PET/CT, and the measuring of the CA-25 level. (Dragosavac et al., 2013)

While CA-25 has the proof of being high sensitivity marker for following up and detection of recurrent as the leveling may reach up to 3 or 6 months before a clinical apparently syndrome could be diagnosed, it usually doesn’t provide us the exact information of sizes of the syndrome. Also, CA-25 may cause elevation in a lot of benignity conditions that also may be of normal incidence in a lot of patients that have the recurrent. (Dragosavac et al., 2013)

FDG PET/CT play a pivotal rolling in the diagnosis of recurrent as the metabolic tracing that increases the chance of the lesion detection by fusing the metabolism and the anatomy that help in determining exactly the locating lesion and doing the survey for whole patient's body. (Dragosavac et al., 2013)

Pathway of Spread/Recurrence in Ovarian Cancer

Ovarian cancer spreading primary through the directly extending neighbor organ (bladder or rectum) or may be when the cancerous cellular detached out of the first tumor. (Lengyel 2010)

Exfoliation of the cellular entity to the peritoneum cavity usually transportation by the physiological peritoneum fluids and also the chance of implantation on parity and visceral peritoneal through the peritoneum cavitation. Due to the hemodynamically peritoneum fluid, the site that usually being involved is the right paraphrenic nerve space, with diaphragm, liver, and Harrison's pouch. (Lengyel 2010)

Tumor spreading with extension to the lymphatic is usually seen in three destinations. The main path of 1ymph node spreading is usually along with broad liegemen and parametric to the pelvis sides lymph nodes (external and internal chains), and also through vessels of the ovary through the upper common and para-aorta lymph among the hilum of the kidney and aorta bifurcation. Draining to the nodes (external and internal) through the rounded ligamentum which accounts for the fastest direction of lymph tumoral spreading. (Lengyel 2010)

Hematological spreading happens lately in the course of the syndrome. Distance between metastases usually seen in liver, pleural, and renal. At time of first presenting liver deposits it is usually very rarely to detect hepatic lesions. (Lengyel 2010)

PET/CT Findings

1. Local pelvic mass

Despite of being uncommon solitary pelvic recurrence in treated ovarian cancer patients could be seen. (Rauh et al., 2017)

Suboptimal cytoreductive surgery may contribute in increasing the number of patients who present with recurrent pelvic mass. About 53 % of ovarian cancer patients who underwent suboptimal debulking presented with recurrence at the same site of the primary tumor. (Rauh et al., 2017)

FDG-avid pelvic masses could be detected on PET /CT in patients with ovarian cancer recurrence. Invasion of the urinary bladder, rectum and even pelvic side wall could be also seen (Fig 5.1). (Gouhar et al., 2013)

(Figure 5.1) Recurrence ovarian cancer in a 49year-o1d patient with ovary carcinoid, histopathological correlation revealing bilaterally ovary granulose cellular carcinoma G2, went TAH&BCO, receiving chemotherapeutic medication. (a and d) Axial enhanced CT, (b and e) FDG and PET, and (c and f) fusion PET/CT imaging showing multiplicity of confluence of soft masses (a–c) are seen posteriorly and superiorly to the urine bladder and partial invagination of rectum and colon, with lower grade FDG and maximum.SOV∼4.5. The lateral rectum(d–f) wall showing thickening and partial inseparability from the left pelvis components of the mentioned masses, findings gives high suggestion of local pe1vis recurrent. Quoted from (Gouhar et al., 2013)

2. Peritoneal Metastases

At PFT/CT, peritoneum implantation seen as nodularity soft masses, often with a variability degree of high metabo1ism activation. Impairment of the lymph draining of peritoneal cavitation, a result of block of diaphragm lymph , plays a very important rolling in the developing ascitic fluid. (Son et al., 2011)

Tumoral cells tend to run with the circulation pathway of peritoneum fluid, implantation in the posterior Douglas pouch , colic gutters, small bowel wall mesenteric, ileocecum junctions, diaphragm surfaces especially the right phrenic spaces along the convex liver and rena1 fossa

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