CT and MRI in pregnancy and lactation Fergus Coakley MD, Professor of Radiology and Urology, Vice Chair for Clinical Services, Chief of Abdominal Imaging,

CT and MRI in pregnancy and lactation

Fergus Coakley MD, Professor of Radiology and Urology,

Vice Chair for Clinical Services, Chief of Abdominal Imaging, UCSF

Learning objectives

Detail the safety issues related to CT and MRI during pregnancy/lactation

Describe the problematic and newer applications of CT and MRI in pregnancy

Advise clinicians on appropriate use of imaging in pregnancy/lactation

Medline hits for “CT radiation dose”

Context

Growing demand and radiation awareness:

– 121% more tests over 10 years

Doctors poorly informed:

– Superficial ACOG guidelines– 5% would suggest TOP after CT

Radiologists need to take the lead

RSNA program 2007; 436AJR 2004; 182: 1107-1109

Safety of CT

Safety of CT - Safety of MRI - Indications for CT and MRI

Risks of CT

Teratogenesis

– Stochastic (threshold) Carcinogenesis

– Non-stochastic (no threshold) Iodinated contrast

Teratogenesis

Unlikely <4 or >17 weeks (organogenesis)– Measured from first day of LMP– Known effects mainly on CNS: Mental/growth

retardation, microcephaly, microphthalmia, cataracts

Estimated threshold dose of 5 to 15 rad– Dose from standard pelvic CT: 1-10 rad– No detected teratogenic effects in human studies

Exposure of the pregnant patient to diagnostic radiations: a guide to medical management. Lippincott 1985; 19-223

AJR 1996; 167: 1377-1379 Radiology 1986; 159: 787-792Br J Radiol 1987; 60: 17-31

Endpoint Risk

Baseline risk of childhood cancer (0-15 yrs) 19/10,000

Excess risk per rad of fetal whole body dose 4.6-6.4/10,000

Relative risk of childhood cancer after 5 rad 2

UNSCEAR 1972 Report to the UN General AssemblyNational Radiological Protection Board, 1993: 15-157

Thrombosis and Haemostasis 1989; 61: 189-196

Carcinogenesis

Basis of risk estimates

Oxford Survey of Childhood Cancer

547 case-control pairs (1953-55):– Child (< 10) dying of cancer in England &

Wales – Matched living control (age, sex, location)– Standard questionnaire to both mothers

OSCC subsequently extended:– 15,276 case-control pairs by 1981

Lancet 1956; 2: 447 BJR Feb 1997; 130-139

Maternal radiation

Controls

Cases Risk

To abdomen 43 85 2.0

To other body part

55 58 1.0

None 447 404 NA

OSCC - Results

Gestational age & carcinogenesis

Relative risk by trimester (OSCC data):

J Radiol Prot 1988; 8: 3-8

First (< 10 weeks)

First(All)

Second Third

4.6 3.2 1.3 1.3

What should we do?

Only perform CT of the pregnant abdomen and pelvis if critical:– Clear clinical justification with benefit >> risk– No non-ionizing imaging options– CT of other body areas much smaller concern

Risks and benefits should be discussed with the patient/parents and documented:– Signed informed consent may be wise– Sample form at www.radiology.ucsf.edu

Parental counseling

Absolute risks:– Baseline risk of fatal childhood cancer = 1/2000– Risk after fetal dose of 5 rads = 2/2000

Practical comparisons for excess risk:– Driving 20,000 miles in a car– Living in New York City for 3 years

ACOG guidelines are superficial:– Describe carcinogenic risk as "very small”– Conclude "abortion should not be recommended”– Do not discuss parental counseling/consent

http://www.physics.isu.edu/radinf/risk.htmObstet Gynecol 2004; 104: 647-651

Imaging fertile women

Varying historical approaches:– 10 day rule, 28 day rule, limited 10 day rule

Largely based on “all or nothing” concept of early risk, and ignores carcinogenesis

What are the regulatory and practical requirements?

Statement from the 1983 Washington meeting of ICRP. Annals of International Commission on Radiological Protection 1984:14 Board statement on diagnostic medical exposure to ionising radiation during pregnancy and estimates of late radiation risks

to the UK population. Documents of the NRPB 1993; 4:1-14

Regulatory guidelines

No requirement for pregnancy testing

ACR: “Radiologists should be advised of known or possible pregnancy”

HHS: “A woman who is or thinks she is pregnant should be encouraged to give this information to the physician”

Medical radiation: a guide to good practice. ACR 1985;4-8DHSS publication no. HHS/FDA-86-8254

AJR 1996; 167: 1377-1379

Good practice

Pregnancy section on requisition forms

Prominent signage

Routine questioning by technologist

Good practice

No safe time during menstrual cycle:– Various “day rules” are obsolete

Any possibility of pregnancy: – Consult with clinician +/- perform pregnancy test

Earliest positive pregnancy test:– Serum hCG - 7 days after conception– Urinary hCG - first day of missed period

STALL!!– Request other opinions, e.g. surgical consult

Inadvertent exposure

17 year old undergoing CT for incidentally discovered FNH - denied any possibility of

pregnancy

Case 1

Inadvertent exposure

Case 2

46 year old - denied pregnancy “irregular periods”

Inadvertent exposure

Case 3

21 year old – post BMT for CML – no periods for 6/12 but denied pregnancy – now with

nausea and cramping

Inadvertent exposure

Case 4

27 year old - denied pregnancy“late period” (5 weeks gestation)

Inadvertent exposure

GESTATIONAL SAC

DECIDUAL REACTION

Case 4

Inadvertent exposure

Case 5

20 year old at 7 weeks gestation with RLQ pain

GESTATIONAL SAC

PLACENTA

CORPUS LUTEUM

Source Fetal dose guideline

Hammer-Jacobsen Advisable if > 10 rad (“Danish rule”)

Wagner et alConsider if > 5 rad at 2 to 15 weeks

Recommend if > 15 rad

Hall Consider if > 10 rad at 10 days to 26 weeks

Danish Med Bull 1959; 6: 113-122Exposure of the pregnant patient to diagnostic radiations: a guide to

medical management. Lippincott 1985; 19-223Radiobiology for the radiologist, 4th ed. 1994: 363-452

Exposure and termination

Fetal doses

Patel, S. J. et al. Radiographics 2007; 27: 1705-1722

Key point: Radiation dose from single CT of the pelvis is highly unlikely to justify termination

Copyright ©Radiological Society of North America, 2007

1 rad 2 rad 3 rad

What about PET?

Rare - two reported cases

Fetal dose estimates vary:– 0.8, 1.2, and 1.5 mGy/mCi– May vary with gestational age

J Nucl Med 2010; 51: 803-5J Nucl Med 2008; 49: 679–82J Nucl Med 2004; 45: 634–5

J Nucl Med 2003; 44: 1522–30

40 year old woman with metastatic breast cancer – “no periods for 5 years” - 12.4 mCi FDG

Fetal dose = 10-19 mGy (1-1.9 rad)

Iodinated contrast in pregnancy

Iodinated contrast should be avoided:– Amniography can cause hypothyroidism– Mutagenic to human cells in vitro

NOT teratogenic in animals

Better than rescanning?

Invest Radiol 1982; 17: 183-185Eur J Radiol 1994; 18 (Suppl 1): 21-31Invest Radiol 1989; 24 (Suppl 1): 16-22

Am J Obstet Gynecol 1976; 126: 723-726

Neonatal hypothyroidism?

23 babies of 21 women:– All had contrast-enhanced CT during pregnancy– No cases of neonatal hypothyroidism

343 babies of 332 women:– All had CECT for PE during pregnancy– No cases of neonatal hypothyroidism (transient

reduced TSH in one)

AJR 2008; 191: 268-71Radiology 2010; 256: 744-50

Iodinated contrast and lactation

Standard recommendation:– Stop breast-feeding for 24 hours

Weak rationale:– Minimal passage of IV contrast into breast milk– Minimal absorption of oral iodinated contrast– No thyroid dysfunction after neonatal IV contrast

Recommendation recently questioned:– Personal approach - continue breast-feeding

Eur J Radiol 1992; 12: 22-25Acta Radiol Suppl. 1980; 362: 87-92

Eur Radiol 2005; 15: 1234-1240

Safety of MRI

Safety of CT - Safety of MRI - Indications for CT and MRI

Risks of MRI

Teratogenesis

Acoustic damage

Gadolinium toxicity

Teratogenesis: Chick embryo study

304 chick embryos

1.5T x 6 hours Controls

19.5% abnormal/dead 10.7% abnormal/dead

JMRI 1994; 4: 742-748

Statistically significant difference

Acoustic damage

Follow-up of 20 children after fetal EPI:

– 16/18 passed hearing test at 8/12 (16.7 expected) Intragastric sound intensity measurement:

– Fetal exposure < maternal

Am J Obstet Gynecol 1994; 170: 32-33Br J Radiol 1995; 68: 1090-1094

Gadolinium toxicity

Teratogenic: Skeletal malformations – 0.5 mmol/kg/day x 13 days to pregnant rabbits– No adverse effect in small human studies– Use only if essential

Omniscan package insert, Nycomed, Princeton, NJRadiology 1997; 205: 493-496 Clin Radiology 2000; 55: 446-453

Radiology 2011; 258: 455-460

Clears rapidly from fetus and amniotic fluid in mice

Category

Fetal dose (rads)

A Controlled studies in women fail to demonstrate a risk to the fetus – remote possibility of fetal harm

BAnimal studies show no risks, but there are no controlled human studiesAdverse effects in animals, but not in well-controlled human studiesUse in pregnancy considered probably safe (e.g. acetaminophen)

CStudies in animals have revealed adverse effects on the fetus and no controlled studies in women, or studies in women and animals not available Only use if benefit justifies the potential risk (most prescribed medications)

DPositive evidence of human fetal riskBenefits may be acceptable if the risk is high (life-threatening situation or serious disease with no other options, e.g., most chemotherapy drugs)

X Studies in animals or women have demonstrated fetal abnormalitiesNot to be used – absolutely contra-indication (e.g., thalidomide)

FDA and drugs in pregnancy

IODINATED CONTRAST

GADOLINIUM

Gadolinium and lactation

Package insert “recommendation”:– Unknown if this drug is excreted in human milk– “Caution should be exercised”

Recent study of 20 lactating women:– < 0.04% of maternal dose passes into milk– Less than 1% of permitted IV neonatal dose

Suspension of nursing not warranted?

Omniscan package insert - amershamhealth-us.comRadiology 2000; 216: 555-558 Eur Radiol 2005; 15: 1234-1240

Indications for CT and MRI

Safety of CT - Safety of MRI - Indications for CT and MRI

Maternal PELVIC EXTRA-PELVIC

Obstetric

Pelvimetry Placenta accretaAdnexal massRed degeneration of fibroidPostpartum uterine mass

Cerebral venous thrombosisPulmonary embolismHELLP syndrome

OtherAcute appendicitisFlank pain

TraumaMalignancy

Indications for CT/MRI in pregnancy

Fetal Mainly MRI of CNS anomalies – some body applications

Pulmonary embolism

PE rate = 0.7 per 1000 pregnancies:– 50% occur after Cesarean section

Imaging options:– V/Q scan, helical CT, pulmonary angiography– No comparative studies in pregnancy– 25% of V/Q scans nondiagnostic in pregnancy

(v. 7% in nonpregnant patients)

Angiology 2002; 53: 429-434Obstet Gynecol 1999; 94: 730-734

Arch Intern Med 2002;162:1170-1175

Test Fetal dose

Helical CT3-130 microGyRises from first to third trimester

V/Q scan100-370 microGy Assumes reduced dose of Tc 99m (37-74 MBq)

Pulmonary angiogram

500 microGyAssumes brachial approach

Radiology 2002; 224: 487-492

Radiation doses from PE studies

Perfusion only scan?

British Medical Journal 2005; 331: 350

Dose CTPA Q scan

Maternal 2.0 Sv 0.6 Sv

Breast 10.0 mGy 0.28 mGy

Fetus 0.01 mGy 0.12 mGy

Acute appendicitis in pregnancy

Major indication for surgery in pregnancy:– 1 in 1500 pregnancies– Diagnosis clinically difficult, 25% perforation rate

Limited data on role of imaging:– CT 100% accurate (n = 2 of 7)– US 100% sensitive & 96% specific (n = 15 of 42)– US could not be performed in 3 (all > 35 weeks)

Mil Med. 1999; 164: 671-674 Am J Obstet Gynecol 2001; 184: 954-957

AJR 1992; 159: 539-542

Appendix hard to see near term

APPENDIX

34 weeks

APPENDIX?

37 weeks

MRI for appendicitis in pregnancy

Dutch study of 12 suspected cases:– Mean gestational age of 17 weeks (range, 7-35)– 3 with surgically proven appendicitis

*17 and 35 weeks gestation

AJR 2004; 183: 671-675

True positive True negative Not seen

US 1 0 11

MRI 3 7 2*

MRI for appendicitis in pregnancy

Beth Israel study of 51 suspected cases:– Mean gestational age of 20 weeks (range, 4-38)– Oral Gastromark/Readi-Cat mix (dark on T1 & T2)– Three planes of SSFSE

Sensitivity of 100%, specificity of 93.6%– Only 4 “proven” appendicitis (3 surgical, 1 CT)– Gestational ages of 13, 20, 27, and 31 weeks

Radiology 2006; 238: 891-899

Normal Positive

MRI for appendicitis in pregnancy

Normal Positive

UCSF experience

TRUE POSITIVE

34 weeks

TRUE NEGATIVE

31 weeks

T2

T1

TRUE NEGATIVE

32 weeks

TRUE NEGATIVE

UCSF experience

?

26 weeks

TRUE NEGATIVE

CT prior to pregnancy

UCSF experienceSMALL BOWEL OBSTRUCTION

18 weeks

FORNICEAL RUPTURE

14 weeks

Flank pain

Hydronephrosis common in pregnancy:– Probably mechanical– Consider stones, etc if

symptomatic

Imaging options:– US, NECT, IVP, isotope

renography, MRU– No established optimal approach

Imaging stones in pregnancy

Incidence: 0.3 per 1000 deliveries

Detection of calculi by first test ( n = 57):– Renal US - 21 of 35 (60%)– AXR - 4 of 7 (57%)– IVP - 13 of 14 (93%)

Estimated fetal doses:– IVP = 1.4 rad– CT = 2.6 rad

Obstet Gynecol 2000; 96: 753-756 Am Fam Physician 1999; 59: 1813-1818

AJR 2002; 178:1285-1286

Examples38 weeks

FORNICEAL RUPTURE 31 weeks

LEFT URETERAL STONE

MRU in pregnancy

Two techniques for MRU:– Static - heavily T2W images– Dynamic (MREU) - serial T1W images

after standard dose of gadolinium– BUT gadolinium is teratogenic!!

Alternative to IVU?– Stones seen in 4/15 patients1

– MREU/MAG3 concordant in 8/9 cases2

1. Magn Reson Imaging 1995; 13:767-7722. Clinical Radiology 2000; 55: 446-453

FSE MRU

Take home points

CT and pregnancy:– Teratogenesis unlikely at diagnostic doses– Carcinogenesis is a real risk– Document risk/benefit discussion, or signed consent

MRI and pregnancy:– No proven risk, but avoid first trimester studies

Contrast and pregnancy/lactation:– Iodinated contrast is (probably) safe– Gadolinium is (relatively) contraindicated– No need to stop breast-feeding

Take home points

Suspected PE in pregnancy:– CT preferred to V/Q scans throughout pregnancy

Suspected appendicitis in pregnancy:– All modalities limited near term - US worth trying– MRI may help if US inconclusive

Flank pain in pregnancy:– US first – but may be indeterminate– Manage symptomatically versus limited IVP?– Remember forniceal rupture

Obstet & Gynecol 2008; 112: 333-340

Case study

20 year with SEVERE flare of known Crohn’s disease at 19 weeks gestation

“Must rule out abscess” - GI attending

CONTRAST-ENHANCED CT

OR

GAD-ENHANCED MRI?

“We’ve created a safe, nonjudgmental environment that will leave your child ill

prepared for real life”