PET/CT & Nuclear Medicine in Clinical Practice

The 8 th | Snowmass 2017: PET/CT & Nuclear Medicine in Clinical Practice

Friday, February 24, 2017 Westin Snowmass Resort • Snowmass Village, Colorado

Educational Symposia TABLE OF CONTENTS

FRIDAY, FEBRUARY 24, 2017

Fluoride PET/CT Bone Imaging (Kevin L. Berger, M.D.)...... 221

Bone Scintigraphy (Andrew T. Trout, M.D.)...... 235

Improving Efficiency in PET/CT Practice (Paul Shreve, M.D.)...... 249

Infection and Inflammation Imaging (Don C. Yoo, M.D.)...... 263

Clinical Molecular Imaging: Beyond FDG and PET/CT (Arif Sheikh, M.D.)...... 275

SAVE THE DATES - 2018 Winter Symposia 221 222 INTRODUCTION DIAGNOSTIC METHODS

Modalities 18F NaF was one of the original • Planar bone scan agents. In fact, FDA • X-Ray • CT approved 18F NaF for clinical use in • MRI 1972. • SPECT/CT • PET • PET/CT

Now, there are many choices to Bone Imaging Agents diagnose a bone metastasis. • 99mTc medronate (MDP) • 99mTc oxidronate (HDP) • 18F FDG • 18F NaF

INTRODUCTION 18 INTRODUCTION HOW DOES F NaF WORK? ADVANTAGES OF 18F NaF PET/CT BONE SCANS

• 18F produced by proton bombardment of 180, represents a precursor in pathway of 18F for FDG production • Combining 18F NaF PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal 18F NaF PET • Fluorine is directly incorporated into bone matrix, converting hydroxyapatite to fluoroapatite similar to Tc99m based bone agents which adhere by chemical but at twice the rate of the phosphonate mechanism leads to faster uptake • Although 18F NaF and 99mTc-diphosphonate have a similar patient dosimetry, 18F NaF PET offers shorter study times improved patient convenience, and faster • Approximately 30% of 99mTc-MDP is protein-bound immediately after injection which turnarounds of reports to the referring physicians. increases to approximately 70% by 24 hours after injection. There is no significant protein binding with 18F NaF.

Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008; 49(1):68-78 Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008; 49(1):68-78

INTRODUCTION TECHNICAL CONSIDERATIONS MORE ADVANTAGES RADIATION EXPOSURE COMPARING 99mTc MDP vs 18F NaF PET

• Faster bone uptake Why use PET/CT with • Rapid clearance3 and low protein 18F NaF for 2 bone binding imaging? • Higher bone to background ratios1,3

• Minimal patient prep

• Shorter study times2

1Schirrmeister, H et al. Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography. J Clin Oncol. 1999; 17(8): 2381-2389 2Frederick, DG et al. Skeletal PET with 18F-Fluoride: Applying New Technology to an Old Tracer. J Nucl Med 2008; 49:68–78. 3Even-Sapir, E et al. The Detection of Bone Metastases in Patients with High-Risk Prostate Cancer: 99mTc-MDP Planar Bone THE SNM PRACTICE GUIDELINE FOR SODIUM 18F-FLUORIDE PET/CT BONE SCANS 1.1 Scintigraphy, Single- and Multi-Field-of-View SPECT, 18F-Fluoride PET, and 18F-Fluoride PET/CT. J Nucl Med 2006; 47:287–297.

223 TECHNICAL CONSIDERATIONS TECHNICAL CONSIDERATIONS 18F NaF FLOURIDE PET SCAN PET/CT BONE SCAN TECHNIQUE PATIENT PREPARATION

18 • No glucose check • 2.22 MBq/kg or 5 - 10 mCi F NaF i.v. • No dietary restrictions • Allow 60 minutes for distribution • No activity restrictions • Pediatric should be weight based • Patient should be well-hydrated (minimum 0.5 mCi and maximum 5mCi) • Have patient show up

TECHNICAL CONSIDERATIONS Will 18F NaF with PET/CT replace PET/CT BONE SCAN TECHNIQUE 99mTc Bone Scintigraphy?

• FDA-approved radiotracer Sodium • Helical CT Attenuation scan Fluoride • 3D Whole Body PET emission scan • Automatic Nuclear and CT correlation (90 - 300 seconds/bed) • High resolution scan • Reconstruct CT in bone algorithm • 3-D tomographic reconstructions

Is 18F NaF PET/CT effective in Planar 99mTc MDP bone scans identifying metastasis?

Patient History • 81 year old male with history of prostate cancer status post irradation presents with elevated PSA and alkaline phosphatase. Outside hospital bone scan reported as normal.

224 Planar 99mTc MDP bone scans 18F NaF

18F NaF with PET/CT How does 18F NaF compare to bone scans?

PET Whole Body Bone Imaging

• ROC Curve was 0.99 for PET and 0.64 for radionuclide bone scintigraphy. In a series of 44 patients, PET identified 96 metastases compared to 46 by bone scan. All lesions found with bone scintigraphy were found by PET

Sensitivity in Detecting Osseous Lesions Depends on Anatomic Localization: Planar Bone Scintigraphy Versus 18F PET by Schirrmeister, J Nucl Med 1999; 40:1623-1629.

Whole Body PET Whole Body PET Bone Scan Bone Scan

Patient History • 74 year-old gentleman with prostate carcinoma and rising PSA

Fluoride PET Bone Scan FDG PET Whole Body Scan

225 Whole Body PET Bone Scan Can you use 3 phase bone scans on PET/CT?

Patient History • 56 year-old woman who is an avid runner complaining of left foot pain

Dynamic PET Bone Scan Dynamic PET Bone Scan

Delayed

Flow

Immediate static

Whole Body Bone Scan Whole Body Bone Scan

• How specific is18 F NaF PET/CT compared Patient History • 52 year-old woman with known metastatic breast cancer to FDG PET/CT for bone metastasis? status post chemotherapy with PET fluoride bone scan and FDG PET scans performed within the same week.

226 Whole Body Bone Scan Whole Body Bone Scan

Fluoride PET Bone Scan FDG PET Whole Body Scan Fluoride PET Bone Scan FDG PET Whole Body Scan

Lower Extremity Comparison Fluoride PET Bone Scan

FDG PET Whole Body Scan

FDG PET 18F NaF PET

CASE STUDY 5 Whole Body PET Bone Scan Lower Extremity 18F NaF PET/CT

Patient history: • 57 year-old gentleman with lung cancer who complains of back pain.

227 Whole Body PET Bone Scan

Whole Body PET Bone Scan Whole Body PET Bone Scan

PET Bone Scans in Pediatrics CASE STUDY 7 PET Bone Scans in Pediatrics

Patient History: • 11 year-old girl with pain distal left leg

228 PET/CT Bone Scans in Pediatrics

Immediate Static

PET/CT Bone Scans in Pediatrics PET/CT Bone scan

Diagnosis: Osteoid Osteoma • 15 year old complains of persistent low back pain

PET/CT Bone Scan

Patient History: • 16 year-old cross-country runner with left leg pain

229 PET/CT Bone Scan PET/CT Bone Scan

PET/CT Bone Scan PET/CT Bone Scan

PET/CT Bone Scan Dual Tracer PET

• Improved sensitivity (97% patients showed equal or greater number of lesions) – EJNM. Prospective comparison of combined 18F-FDG and 18F NaF PET/CT vs 18F-FDG PET/CT imaging for detection of malignancy from Lin et al.

Freibergs Infraction

230 Dual Tracer PET Case example

• Decreased radiation dose (largely secondary • 63 year-old male status post left radical to less CT component) neck dissection for parotid carcinoma. • Patient convenience with more rapid staging turnaround

– JNM 2012; 53:586 Evaluation of NaF PET/ CT, FDG PET/CT, combined NaF/FDG PET/ CT and CT alone for detection of bone metastases by Sampath et al.

Dual NaF/FDG PET/CT Dual NaF/FDG PET/CT

Dual Tracer PET Dual Tracer PET

• Improved sensitivity (97% patients showed • Decreased radiation dose (largely secondary equal or greater number of lesions) to less CT component) – EJNM. Prospective comparison of combined • Patient convenience with more rapid 18F-FDG and 18F NaF PET/CT vs 18F-FDG staging turnaround PET/CT imaging for detection of malignancy from Lin et al. – JNM 2012; 53:586 Evaluation of NaF PET/ CT, FDG PET/CT, combined NaF/FDG PET/ CT and CT alone for detection of bone metastases by Sampath et al.

231 Dual NaF/FDG PET/CT

63 year-old male status post left radical neck dissection for parotid carcinoma.

Dual NaF/FDG PET/CT

Reimbursement & Coding

NOPR GUIDELINES NOPR GUIDANCE INITIAL TREATMENT STRATEGY SUBSEQUENT TREATMENT STRATEGY

18F Fluoride PET performed as part of an evaluation for determination of an initial 18F Fluoride PET is also covered by CMS only with participation in this registry when used in treatment strategy is covered by CMS only with participation in this registry. 18F fluoride PET subsequent treatment strategy to identify bone metastases in a patient with a pathologically may be used both for diagnosis of strongly suspected bone metastases in a patient without a proven cancer. pathologically proven diagnosis of cancer and as part of initial staging in a patient with a pathologically proven cancer. 18F Fluoride PET is covered for restaging and detection of suspected recurrences: 1. After completion of treatment for the purpose of detecting residual disease; or Note: 18F Fluoride PET is covered only in clinical situations in which: 2. For detecting suspected recurrence or metastasis; or • The PET results may assist in avoiding an invasive diagnostic procedure 3. To determine the extent of a known recurrence: • The PET results may assist in determining the optimal anatomical location to perform an invasive 4. If it could potentially replace one or more conventional imaging studies when it is expected that diagnostic procedure. In general, for most solid tumors, a tissue diagnosis is made prior to doing conventional study information is insufficient for the clinical management of the patient. a PET bone scan and the therefore the scan is performed for staging rather than diagnosis. 5. Restaging applies to testing after a course of treatment is completed, and is covered subject to the • PET is not covered as a screening test (i.e., testing patients without specific signs and symptoms conditions above. of disease).

Comment: As noted above, 18F Fluoride PET is not covered as a screening test (i.e., testing patients without specific signs http://www.cancerpetregistry.org/ and symptoms of disease) and thus is not covered for surveillance of patients treated for cancer in whom there is no clinical reason to suspect recurrent disease http://www.cancerpetregistry.org/

232 NOPR GUIDELINES PET PHYSICIAN SCAN ASSESSMENT FORM

OVERALL ASSESSMENT • Normal study • Benign skeletal abnormalities only • Osseous metastatic disease or primary malignant bone tumor • Unifocal • Multifocal • Diffuse skeletal involvement

If osseous metastatic disease or primary malignant bone tumor selected, indicate level of confidence • Definitely present • Probably present • Equivocal

http://www.cancerpetregistry.org/

NOPR GUIDELINES NOPR GUIDELINES PET PHYSICIAN SCAN ASSESSMENT FORM PET PHYSICIAN SCAN ASSESSMENT FORM

WAS COMPARISON MADE WITH PRIOR RADIONUCLIDE BONE IMAGING? Yes Based on the comparison, there has been: No • No change; there is no evidence on prior or current study of

If yes, indicate type of study: metastatic disease Conventional bone scintigraphy • Resolution of previously seen metastatic disease F-18 fluoride bone PET • Improvement of previously seen metastatic disease Date of prior study • No change in previously seen metastatic disease

• Progression of previously seen metastatic disease http://www.cancerpetregistry.org/

PET BONE SCAN CODING PET BONE SCAN CODING

• Effective January 1, 2008 the AMA CPT PET and PET/CT codes • For third-party payers who cover PET bone scans, choose changed by removing the word "tumor" to allow a broader appropriate CPT: 78811-78816 use that would include Positron Emission Tomography (PET) • For radiopharmaceutical, providers should report A9580 bone imaging using 18F fluoride. Sodium Fluoride F-18, diagnostic, per study dose, up to 30 millicuries. – SNM Practice Management Coding Corner

– SNM Practice Management Coding Corner

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247 248 249 250 Big Squeeze Improving Efficiency in PET/CT Practice More to do. Less time and reimbursement to do it

• Comfortable margins in healthcare are passing • Healthcare systems are squeezing everywhere to do more with less FTE and less capital equipment • Bundled reimbursement linked to outcomes next Paul Shreve, M.D. Advanced Radiology Services, P.C • Physician time increasing consumed by regulatory Spectrum Health Lemmen-Holten Cancer Center compliance and administrative mandatory tasks Grand Rapids, MI USA

PET/CT & Nuclear Medicine in Clinical Practice 2017 Burwell, S.M., NEJM 2015; www.nejm.org/doi/full/10.1056NEJMp1500445 Smowmass, CO February 24, 2017

Improving Efficiency in PET-CT

Two General Areas of Focus

• Technical: Doing the PET-CT scans • Professional: Interpretation and reporting PET-CT exams as well as tumor board and multi-specialty clinic participation, and direct physician consultation, peer to peer pre-authorization from payers…..

251 Improving Efficiency in PET-CT Improving Efficiency in PET-CT

Doing the PET-CT Scans What is Efficiency Anyway?

• Number of scans per FTE technologist • Scheduling and pre-authorization • Number of scans per day • Patient education prior to scan • Minimal scanning backlog • Initial patient prep and uptake phase • Maximum utilization of capital equipment • Scan procedure • Total turn around time for exams • Post scan patient management

• Patient satisfaction follow up Metrics Trap: Administration latches onto metrics that are readily available or easily mined but may have nothing to do with actual value to patient and referring physicians

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

Is Fast, Good and Cheap Possible? Scheduling and pre-authorization

• More patients through with same or • Scheduling can be performed by PET-CT less FTE for all involved staff, at department level or at “central • Maintain quality of scans scheduling”- all services of the institution • Maintain quality of patient experience • Most effective if done in PET-CT staff, • Maintain flexibility of patient but that uses staff FTE time population (inpatient, RT, pediatric) • Pre-authorization eats up referring • Maintain flexibility in scheduling (same physician and PET-CT staff FTE time: day scans, patient punctuality issues) • Any arrangement to minimize “pre auths” improves efficiency for all involved

Improving Efficiency in PET-CT PET-CT Information for Patient: Mailing

Patient Education Prior to Scan

• Make sure patient understands what fasting prior to scan really means • Managing fasting in diabetics • Pre-check for anxiety/claustrophobia • Pre-check for special needs (oxygen) • This can be done by nurse or other trained staff rather than technologist • Mailings and web pages help, but no substitute for direct phone contact

252 Improving Efficiency in PET-CT PET-CT Protocoling

Protocoling Data to technologist for protocoling PATH • One protocol does not fit all for optimal scan • Limited coverage, torso, whole body • Special protocols for head and neck, lung nodules OUTSIDE Protocoling Triad Imaging Office note/ • Special patient prep for diabetics, contrast use consult Reports • Inpatient, pediatric, RT all require additional Creatinine values within 30 days involvement of staff and ancillary personnel for eGFR calc. • Requires technologist and physician team effort but is time well spent for overall quality • “80% time spent on 20% of patients” Key task is getting all information needed for scan protocol and scan interpretation

Paper-less Protocoling: Moving to EMR

253 Fax Server Interface for PET-CT Order Optimal Protocoling Tools Receipt, Protocoling, and Scheduling

• Document management software-fax server all orders come to same place “ordering clearing house” • “PACS unchained!”: Online PACS allows distribution to laptops and tablets • HIS/RIS/EMR/HER (data mining) • eGFR calculator (on line apps)

PET-CT Referral Life Cycle

Imaging, PET-CT Referral arrives interpretation& in fax server from patient follow patient’s Provider up with Provider

Authorization & Protocoling PET-CT (concurrent) Scheduled Appeal of with Patient referral if denied

Improving Efficiency in PET-CT

Patient Prep and Scanning

• Challenge is to maintain patient sequencing while accommodating mishaps (urinary voiding, emesis) and specific protocol needs (inpatient, RT, pediatric) • There is only so much wiggle room in the sequence before scan quality and patient experience are compromised • Balance must be found between patient throughput, staff time and patient compliance and comfort

254 Patient Sequencing

Tracking Patient Satisfaction Improving Efficiency in PET-CT

PET-CT Scanning Operations

Scanner: Technologist: performs scans, monitors image recon and archiving, monitors uptake room, fields calls, just in time protocolling

Prepper: Technologist/RN: Interviews patient, establish IV/port access, infuses FDG, Invoked new schedule meds, hydration, helps with protocoling

Flipper: Ancillary person: Moves patient to and from uptake room to scanner room, positions patient in scanner, check IV, handles discharge instructions

Making efficiency consistent & convenient: Improving Efficiency in PET-CT nomogram for PET emssion time & IV contrast

Scanning Operation Efficiencies If patient is at risk for CIN, administer the next lowest amount of contrast, i.e., if the patient would have received 125 mL and is @ risk for CIN, then administer 100 mL. • Shortening uptake time for first patient (65 minutes rather than 90 minutes) Patient’s @ > risk for CIN:

• Renal insufficiency: eGFR between 30 & • Have dedicated “flipper” and “scanner” 60 mL/min • H/o nephrotoxic medications (loop diuretic, aminoglycosides, NSAIDs, • Shared RNs for port access and meds cisplatinum • DMII • Sickle Cell • Adjust emission time for body size • Multiple Myeloma • Solitary kidney • Streamline Head and Neck protocol • Prior I.V. contrast < 48 hours • Automate archiving

Note: Like most tools, this nomogram is only applicable for most patients. It is not well-suited to extremes, i.e. very tall, very short, or pediatric patients.

255 Streamlining Head and Neck Cancer PET-CT Protocol Improving Efficiency in PET-CT

Arms down Arms up

Scanning Operation Efficiencies

Dedicated Neck Dedicated Chest CT and neck PET CT and PET • Shortening uptake time for first patient (65 minutes rather than 90 minutes) • Have dedicated “flipper” and “scanner” • Shared RNs for port access and meds • Adjust emission time for body size Arms down Arms down • Streamline Head and Neck protocol • Automate archiving

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

Scanning Operation Efficiencies: Automatic Archiving Scanning Operation Efficiencies: Automatic Archiving • Image sets for routine interpretation • Autotransfer of images sets requires adequate + network bandwidth – data constipation will slow • Anticipated image sets for special down entire operation applications • We retain the raw data sets for a few days in case additional image reconstructions are needed - Thin section breath hold lung algorithm recontruction • Archiving can be to PACs, interpretation for navigation bronchoscopy “Super D” workstation and off-line drives – we archive images sets to PACs as we use PACs workstation -3 x 3 mm full FOV for RT planning software import for all our image interpretation

- Fusion image sets specific for clinician needs

256 Improving Efficiency in PET-CT

Interpretation and Reporting PET-CT

• PET-CT exams among most complex and time consuming to interpret and report • Follow up therapy scans typically more work than initial staging, and these are increasing • Tumor boards/multi-specialty clinics participation increasingly mandatory • Metrics can challenge quality • Professional reimbursement low for actual interpretation workload of a PET-CT scan

One solution for burnout: Improving Efficiency in PET-CT (actual view from office)

Strategies and Tools for Interpretation Efficiency

• PACS and dedicated workstations • RIS/HIS access to patient records, particularly prior imaging, pathology and clinic notes • Have relevant path reports, clinic notes, outside imaging reports scanned into to PACS at time of protocoling (protocol triad)

257 PACS Scanned Documents Improving Efficiency in PET-CT

PET-CT Reporting

• Voice recognition is a love-hate relationship • At the least exam type, date, history and procedure can be auto-filled. • Auto-filled history usually inadequate for a quality PET-CT report. We have been seeing eneralized ICD-10 codes, abbreviations, miss- spelled words

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT Reporting: Auto-fill History Digging out an adequate history takes time

Auto-fill history: LYMPHOMA • Path reports very useful • Clinic notes can be useful but also can contain miss-information, “cut and paste” errors Appropriate History: Follicular B-cell lymphoma diagnosed 6 months prior on • Prior imaging reports – a concise and complete inguinal lymph node excisional history in an imaging report a worthwhile investment biopsy. Initial stage IIIa. Now post 6 cycles of chemotherapy, • Increasingly with ICD-10 great deal of history last dose two weeks prior. For is required – the more ICD-10 codes your coders have the better odds of getting paid restaging of lymphoma

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT Reporting: Voice Recognition Proofreading PET-CT Reporting Templates

Recent ultrasound report: …“mild prominence of • Some physicians find templates helpful in the mid buttocks” organization of PET-CT report • Templates in findings section slow some physicians down and take focus off the images …mild prominence of • Detail of template report is a personal pref the mid bile duct.

258 Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT, RVUs, and You PET-CT, RVUs, and You • PET-CT CPT codes describe physician workload as not involving CT interpretation • Since quality is difficult to measure in a meaningful way, management looks for easy • CT is used to make fusion image for “anatomic metrics to fill their bar graphs and pie charts localization” Someone else interprets the CT scan, maybe performed separately, and • Your “efficiency” becomes RVUs generated compares with prior CTs, ect per month, week, day, or even hour • Actual practice is combined anatomic-metabolic • PET-CT is RVU quicksand – often complicated imaging in one procedure and interpretation – patients, complicated histories, lots of this was the intent of the inventors of PET-CT * comparison studies, a flawed CPT code * Townsend DW. Combined PET-CT: The historical perspective. Semin Ultrasound CT MRI 29:232-235 2008.

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT, RVUs, and You PET-CT, RVUs, and You

Professional reimbursement to technical reimbursement 2015 Medicare Professional Reimbursement Loc 99: ratio based on 2015 Medicare Reimbursement Loc 99:

PET/CT whole torso $122.38 PET/CT whole torso 10.3%

CT C/A/P $153.03 CT C/A/P 43.1%

CT N/C/A/P $221.86 CT N/C/A/P 43.7%

Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT, RVUs, and You PET/CT RVUs

• PET-CT CPT codes came out we went to our • Scan the patient twice, one “non-diagnostic for AC private payors and medicare carrier and and localization purposes only” and one C/A/P explained the codes do not describe what we “diagnostic CT with contrast” consider good practice (ie reading CT and PET in integrated fashion, no 2nd CT sans) • Do PET/CT and “diagnostic” CT on separate days • The PET-CT codes did account for the cost of • Do PET/CT with one optimized CT and only charge performing the CT on the technical side, but CT for interpretation (26 modifier) not actually interpreting CT on professional Or…. • Payers generally insist if you have a PET-CT scanner you have to use the PET/CT CPT codes • Work twice as fast when reading PET-CT scan

259 Improving Efficiency in PET-CT Improving Efficiency in PET-CT

PET-CT and RVUs Conclusions

• Efficiencies can be gained in several aspects of “Fast is ﬁne, but accuracy is ﬁnal” performing PET-CT exams • …but hospital administration should be reminded there is no such thing as fast, good and cheap Wyatt Earp 1888 • Some innovations in IT could improve efficiency of interpretation and reporting. • …but sacrifice of value in our interpretation and reporting at the alter of RVU metrics is at our own peril as imaging physicians

260 261 262 263 264 Disclosures Infection and Inflammation Imaging

Don C Yoo, M.D. The author does not have a financial Associate Professor of Radiology (Clinical) interest or other relationship with a The Warren Alpert Medical School of Brown University commercial organization that may have Director of Nuclear Medicine, The Miriam Hospital an interest in the content of the educational activity

Types of Imaging for 3 Phase Bone scan Infection/Inflammation 3 phase bone scan Technique Indium-111 oxine labeled WBC Inject I.V. Tc-99m HMPAO labeled WBC 1 minute blood flow (if needed) Gallium-67 Citrate 5-10 minute immediate static (if needed) PET/CT 3 hour delayed statics

5 year old bit in hand by a dog 2 weeks ago with fever, redness and pain

Osteomyelitis base of proximal phalanx of index finger

265 54 year old man with diabetes and ulcer near right great toe

ANT POST

Pearls:

3-phase bone scan for infection Very sensitive, Not specific

- Osteomyelitis - Fracture - Malignant bone tumor

Osteomyelitis es4613

266 Differential Diagnosis

Fracture Loosening of orthopedic hardware Normal post-operative appearance Osteomyelitis and cellulitis

3-Phase bone

3-Phase bone In-111- WBC scan 3-Phase bone In-111- WBC scan Sulfur Colloid

267 Diagnosis Teaching Points Three phase bone scan Osteomyelitis and cellulitis Highly sensitive for osteomyelitis in 'pristine‘ non-violated bone

Sensitivity decreases in the setting of trauma or intervention/surgery due to expected osteoblastic activity in injured or repairing bone.

Teaching Points

Radiolabeled WBC can increase specificity. Marrow scan can be helpful.

Longer delay or 4th phase (24 hr) images may be helpful to establish osseous localization

Negative perfusion phase -> infection very unlikely

In-111- WBC scan – Right Knee Prosthesis

Tc-99m-Sulfur Colloid

In-111- WBC scan In-111- WBC scan

268 Teaching Points Teaching Points Labeled WBC Imaging In-111 or Tc-99m-HMPAO labeled WBCs Tc-99m-Sulfur Colloid - 'marrow road map‘ Very sensitive and specific for acute osteomyelits in Improves specificity of WBC imaging. non-violated bone (90-95%). Differentiate marrow 'hot spots' which may More sensitive for acute infection develop at the distal end of long bone prostheses WBCs localize to normal marrow elements besides infection Can be performed same day of In-111-WBC scan Normal marrow can become redistributed following -Image different energy windows prosthesis placement, injury, surgery

99mTc-HMPAO WBC Hexamethyl propylene amine oxime 111In-WBC Normal Distribution Spleen >> Liver > Marrow No renal activity No GI activity

Helpful findings Hot spleen Relatively low-count study

4 Hour 19 Hour

Gallium

269 Gallium Scan

Lacrimal Glands!! Low counts Marrow activity Liver uptake > spleen Bowel uptake

Case based Review of Applications of PET/CT for Infection and Inflammation

60 year-old woman with a history of breast cancer status-post lumpectomy in 1997, hypothyroidism, rheumatoid arthritis, irritable bowel syndrome, and chronic fatigue syndrome was admitted to the hospital for hypercalcemia

elevated serum calcium of 11.1 mg/dL decreased albumin of 2.5 g/dL suppressed parathyroid hormone (PTH) of 6 pg/mL elevated angiotensin converting enzyme (ACE) of 93 U/L and elevated C reactive protein (CRP) of 13.4 mg/L

270 Teaching Points:

Symmetric periarticular distribution suggests rheumatoid arthritis

PET activity correlates with disease activity

Rheumatoid nodules in the lung can have variable activity on PET

Fever Without Source (FWS) Whole Body Imaging

Common problem among all ages worldwide • Nuclear medicine can provide WB imaging

FWS = Febrile illness without localizing signs or • Often last resort when initial studies and initial obvious etiology workup negative or equivocal Fever of unknown origin (FUO) is a subtype of FWS defined as fever on several occasions and • Can detect pathologic changes early in illness lasting longer than 3 weeks after disease course even in absence of appropriate workup anatomic abnormality

Most common etiology of FWS: Infection • PET/CT for ID’ing source of fever Etiologies of FUO: Sensitivity: 89-100% Infection Specificity: 23-87% (nonspecific) Neoplasm -infection/inflammation/malignancy Inflammatory Disease

PET/CT for Infection CMS Reimbursements

• Not reimbursed by CMS Ambulatory Payment Modality Classification Fee Professional Fee CXR • We use it at RIH in inpatients with 62.80 9.57-11.40 CT Chest suspected infection, negative initial 138.49-272.66 52.97-65.10 workup CT A/P 264.77-427.21 91.21-95.21 US • Bundled payments, 147.36 42.31 MRI radiopharmaceutical cost 322.80-467.02 76.13-90.46 differences Gallium-67* 719.41 43.38 Indium-111 WBC* 719.41 43.38 Tc -99m WBC* 719.41 43.38 FDG PET/CT Not reimbursed for FWS Not reimbursed for FWS

*Abscess Imaging Whole Body

271 Radiopharmaceutical Costs Cost Analysis

Bundled payments increase need for cost Study Radiopharmaceutical Cost effectiveness analyses including study costs to the hospital or radiology department Ga-67 2X

In-111 WBC 8.8x (most expensive) Costs to perform studies may differ greatly although studies’ efficacies in establishing Tc -99m WBC 8.1x diagnoses may be similar PET/CT x (least expensive) In addition to equipment and labor costs, cost analyses should include radiopharmaceutical costs.

PET/CT for Fever Fever of Unknown Origin

Radiopharmaceutical cost for PET/CT is Meta-analysis: much lower than that for In-111 or Tc-99m Dong MJ et al, Eur J Radiol 80:834-844 (2011) tagged WBC studies

Per-study labor costs, equipment costs, and • 5 studies FDG-PET only (n=214) effectiveness in identifying sources of fever • 4 studies FDG-PET/CT (n=174) are similar, so we perform PET/CT for inpatients with a diagnosis of fever without source

Fever of Unknown Origin

Meta-analysis: Dong MJ et al, Eur J Radiol 80:834-844 (2011)

Initial PET

Sensitivity Specificity AUC

FDG-PET .826 .578 .810

FDG-PET/CT .982 .859 .947

6 month FU PET

272 SUMMARY

Reviewed 3 phase bone scan, Indium-111 oxine labeled WBC, Tc-99m HMPAO labeled WBC, Gallium-67 Citrate

PET/CT can be helpful in evaluating FUO and may be more cost-effective than tagged leukocyte studies because of the large difference in radiopharmaceutical costs

New applications for FDG-PET in evaluating T12-L1 Osteomyelitis inflammation / infection

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