Imaging Brown Adipose Tissue
Michael Lin, Harvard Medical School Year III
Gillian Lieberman, MD
July 2011Michael Lin, HMS IIIGillian Lieberman, MD
PETCTOverlay
BIDMC PACS, coronal C-
chest, abdominal, and pelvic PET-CT
2
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological PET-
CT imaging
•
Abbreviations:
–
BAT: brown adipose tissue
–
C-: without intravenous contrast
–
FDG: 18F-fluorodeoxyglucose
–
PET-CT: positron-emission tomographic and computed tomographic scan
–
UCP1: uncoupling protein 1
Michael Lin, HMS III
Gillian Lieberman, MD
3
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological PET-
CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
4
Index Patient: Clinical Presentation
•
60 year old female with HIV and HCV
•
Now has locally invasive squamous cell carcinoma of bladder
•
PET-CT ordered to evaluate for lymph node involvement and
metastases, surgical planning
Michael Lin, HMS III
Gillian Lieberman, MD
5
Index Patient: Bladder on Coronal PET-CT
•
FDG avidity in region of known bladder carcinoma mass
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
PET CT Overlay
Coronal C-
abdominal and pelvic PET-CT
6
Index Patient: Bladder on Axial PET-CT
•
FDG avidity in
region of known
bladder
carcinoma mass
(less avid) and
bladder lumen
(more avid)
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
PET CT Overlay
PET CT Overlay
Axial C-
pelvic PET-CT
7
Index Patient: Coronal PET-CT
•
FDG in bladder carcinoma and left renal collecting system
•
What about the bilateral supraclavicular and paravertebral
areas
of FDG avidity?
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
PETCTOverlay
Coronal C-
chest, abdominal, and pelvic PET-CT
8
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological
PET-CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
9
What is Brown Adipose Tissue (BAT)?
•
Significant depots in anterior neck to thorax (cervical,
supraclavicular, superior mediastinal depots)
•
High number of mitochondria relative to white adipose tissue
•
Expresses uncoupling protein 1 (UCP1) that mediates non-
shivering thermogenesis by dissipating mitochondrial proton
gradient
•
Found in rodents and young humans, previously thought not to
be physiologically relevant in adult humans
Michael Lin, HMS III
Gillian Lieberman, MD
Cannon and Nedergaard, 2004; Cypess et al., 2009
10
Who Has BAT?
•
7.5% of women and 3.1% of men
–
Other PET-CT studies reported 25% (Döbert et al., 2004) to > 80% of
patients (Rousseau et al., 2006)
–
Autopsy series found BAT in necks of 26/31 patients over age 20
(Heaton, 1972)
•
Women have greater mass of brown adipose tissue (median
12.3 g vs. 11.6 g) and higher FDG uptake activity
•
Probability of detection inversely correlated with age, outdoor
temperature at scan time, beta-blocker use, body-mass index
Michael Lin, HMS III
Gillian Lieberman, MD
Cypess et al., NEJM, 2009
11
Importance of BAT
•
To radiologists and oncologists:
–
High FDG avidity can cause confusion when evaluating tumors using
PET-CT scans
–
Mistaking BAT for cancer metastasis may alter clinical decision making
(e.g., whether to treat cancer surgically)
•
To endocrinologists:
–
Mediator of metabolism and energy balance
–
Potential to be harnessed to control weight
•
Historically, PET was done without concurrent CT
–
Cervical and supraclavicular areas of FDG avidity were thought to be
muscle
Michael Lin, HMS III
Gillian Lieberman, MD
12
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological
PET-CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
13
PET-CT Basics
•
Most common radiotracer, FDG, has radioactive fluorine
attached to glucose, half-life of 110 minutes, emits positrons
–
Other radiotracers have carbon-11, nitrogen-13, oxygen-15
•
One hour after intravenous FDG, non-contrast CT images
obtained, then series of PET images obtained
•
Metabolically active tissue (e.g., tumor) absorbs more glucose
than do other tissues
•
Positron encounters electron, annihilation produces two photons
moving in opposite directions that are detected by PET machine
scintillator
•
CT images co-registered and overlaid with PET images to assist
with anatomic localization of tracer uptake
Michael Lin, HMS III
Gillian Lieberman, MD
14
Physiology of Identifying BAT by PET-CT
•
Body can not metabolize FDG the way it would metabolize
normal glucose because 18F substituted for 2’OH
•
Phosphorylation normally prevents glucose from leaving cell,
FDG is similarly phosphorylated, trapped, accumulated in cells
•
Most intense areas of normal uptake: brain, myocardium, liver,
kidneys, urinary bladder (FDG is renally excreted)
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS Coronal C-
chest, abdominal, and pelvic PET-CT
PETCTOverlay
15
Criteria for Identifying BAT
•
Putative BAT:
–
Collections of tissue > 4 mm in diameter
–
Density of adipose tissue on CT (-250 to -50 Hounsfield units)
–
Maximal standardized uptake values* of 18F-FDG ≥
2.0 g/mL (high
metabolic activity)
–
Symmetric body distribution (vs. asymmetric distribution of metastases)
•
Confirm by detecting UCP1 by immunostaining and RT-PCR
on biopsy specimens from cervical and supraclavicular regions
•
*Standard uptake value: decay-corrected activity per mL within
region of interest divided by injected dose in megabecquerels
per gram of body weight
Michael Lin, HMS III
Gillian Lieberman, MD
Cypess et al., NEJM, 2009; Virtanen et al., NEJM, 2009
16
Other BAT Imaging Modalities
•
18F-FDG PET-CT is modality of choice, others rarely used
•
MIBG (metaiodobenzylguanidine, a noradrenaline analog)
•
Technetium (99mTc) sestamibi (indicator of vascular perfusion)
•
PET-MRI
Michael Lin, HMS III
Gillian Lieberman, MD
17
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological
PET-CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
18
Back to the index patient…
Michael Lin, HMS III
Gillian Lieberman, MD
19
Index Patient: Supraclavicular BAT
on Axial and Coronal PET-CT
Michael Lin, HMS III
Gillian Lieberman, MD
Supraclavicular adipose
tissue density
Symmetric supraclavicular distribution of high FDG avidity
Coronal C-
chest, abdominal, and pelvic PET-CT Axial C-
chest CT
PETCTOverlay
20
Companion Patient #1: Clinical Presentation
•
67 year old female with carcinosarcoma of uterus status post
hysterectomy and bilateral salpingo-oophorectomy
•
Now presenting with large retroperitoneal mass, has had 4
cycles of paclitaxel and carboplatin chemotherapy
•
PET-CT ordered to evaluate treatment response, FDG avidity
seen in pelvic area and neck
Michael Lin, HMS III
Gillian Lieberman, MD
21
Companion Patient #1: Axial PET-CT
•
FDG avid pelvic mass
consistent with known recurrence of
uterine carcinosarcoma, supraclavicular BAT
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
Axial C-
pelvic PET-CT
PETCTOverlay
22
Companion Patient #1: Lateral PET-CT
•
FDG avidity helped identify secondary neoplastic involvement
of L5 vertebra
in an area not classically associated with BAT
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
Sagittal C-
chest, abdominal, and pelvic PET-CT
PET CT Overlay
23
Companion Patient #2: Clinical Presentation
•
54 year old female with 2 months of mid-back pain radiating to
right side
•
Chest X-ray followed by CT chest revealing left lower lobe
1.7cm lung nodule with mediastinal and hilar adenopathy and
T9 fracture
Michael Lin, HMS III
Gillian Lieberman, MD
24
Companion Patient #2: Lung Cancer with
Metastases and BAT on Axial PET-CT
Michael Lin, HMS III
Gillian Lieberman, MD
BIDMC PACS
BAT
FDG avid left lower lobe
lung nodular opacities
Extensive mediastinal, hilar,
and supraclavicular FDG avid
lymphadenopathy
FDG avid right iliac bone
sclerotic metastasis
FDG avid adrenal gland
uptake, likely metastasis
Normal physiologic FDG
uptake in brain, kidneys, and
bladder
Axial C-
abdominal PET-CT
PETCTOverlay
25
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological
PET-CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
26
Companion Patient #3: An Unusual
Location for BAT on Axial PET-CT
•
75 year old female with esophageal cancer, initial staging
•
Lipomatous hypertrophy of interatrial septum
(Fan et al., 2005)
•
Notice corresponding adipose tissue density on CT
Michael Lin, HMS III
Gillian Lieberman, MD
Courtesy J. Anthony Parker, MD PhD
Axial C-
chest PET-CT
27
Agenda
•
Meet index patient
•
Introduction to brown adipose tissue (BAT)
•
Introduction to PET-CT imaging of BAT
•
Typical examples of patients with BAT
•
An atypical presentation of BAT
•
Methods for minimizing interference from BAT in oncological
PET-CT imaging
Michael Lin, HMS III
Gillian Lieberman, MD
28
Methods to Decrease BAT FDG-avidity
•
Important because BAT FDG avidity decreases availability of
FDG to possible tumors, decreases sensitivity of PET
•
Increase temperature of imaging room
•
High-fat, low-carbohydrate diet the night before imaging
•
Benzodiazepines (diazepam, lorazepam)
•
Propranolol
•
Fentanyl
•
Avoid nicotine
Michael Lin, HMS III
Gillian Lieberman, MD
Williams and Kolodny, 2008
29
Summary
•
BAT is present in adults, not just newborns and rodents
•
High metabolic activity allows BAT to be visualized by PET
•
Must take BAT’s high FDG avidity into account on PET-CT
used for oncological evaluation –
not all “hot spots”
are
metastases
•
Concurrent CT with PET aids in anatomic localization,
distinction between BAT and cancer metastasis
•
Many methods of decreasing BAT FDG avidity
Michael Lin, HMS III
Gillian Lieberman, MD
30
References
•
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance.
Physiol Rev. 2004 Jan;84(1):277-359. Review.
•
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL,
Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose
tissue in adult humans. N Engl J Med. 2009 Apr 9;360(15):1509-17.
•
Döbert N, Menzel C, Hamscho N, Wördehoff W, Kranert WT, Grünwald F. Atypical thoracic
and supraclavicular FDG-uptake in patients with Hodgkin's and non-Hodgkin's lymphoma. Q
J Nucl Med Mol Imaging. 2004 Mar;48(1):33-8.
•
Fan CM, Fischman AJ, Kwek BH, Abbara S, Aquino SL. Lipomatous hypertrophy of the
interatrial septum: increased uptake on FDG PET. AJR Am J Roentgenol. 2005
Jan;184(1):339-42.
•
Heaton JM. The distribution of brown adipose tissue in the human. J Anat. 1972 May;112(Pt
1):35-9.
•
Rousseau C, Bourbouloux E, Campion L, Fleury N, Bridji B, Chatal JF, Resche I, Campone M.
Brown fat in breast cancer patients: analysis of serial (18)F-FDG PET/CT scans. Eur J Nucl
Med Mol Imaging. 2006 Jul;33(7):785-91.
•
Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J,
Savisto NJ, Enerbäck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J
Med. 2009 Apr 9;360(15):1518-25.
•
Williams G, Kolodny GM. Method for decreasing uptake of 18F-FDG by hypermetabolic
brown adipose tissue on PET. AJR Am J Roentgenol. 2008 May;190(5):1406-9.
Student Name, year
Gillian Lieberman, MD
31
Acknowledgements
•
Johannes Roedl, MD
•
J. Anthony Parker, MD PhD
•
Gillian Lieberman, MD
•
Emily Hanson
Michael Lin, HMS III
Gillian Lieberman, MD
Imaging Brown Adipose Tissue
Agenda
Agenda
Index Patient: Clinical Presentation
Index Patient: Bladder on Coronal PET-CT
Index Patient: Bladder on Axial PET-CT
Index Patient: Coronal PET-CT
Agenda
What is Brown Adipose Tissue (BAT)?
Who Has BAT?
Importance of BAT
Agenda
PET-CT Basics
Physiology of Identifying BAT by PET-CT
Criteria for Identifying BAT
Other BAT Imaging Modalities
Agenda
Back to the index patient…
Index Patient: Supraclavicular BAT on Axial and Coronal PET-CT
Companion Patient #1: Clinical Presentation
Companion Patient #1: Axial PET-CT
Companion Patient #1: Lateral PET-CT
Companion Patient #2: Clinical Presentation
Companion Patient #2: Lung Cancer with Metastases and BAT on Axial PET-CT
Agenda
Companion Patient #3: An Unusual Location for BAT on Axial PET-CT
Agenda
Methods to Decrease BAT FDG-avidity
Summary
Slide Number 30
Acknowledgements