Advances in Gated MRA of the Thoracic Aorta Using Blood Pool

Agents

Jeffrey H. Maki, MD, PhD, FSCBTMR Director of Body MRI, Professor of Radiology

University of Washington, Seattle, WA

Disclosures – Jeffrey H. Maki

• Speaker’s Bureau Lantheus Medical • Research Support Bracco Diagnostics • Consultant Bayer Healthcare

• Will discuss “off label” use of

Gadofosveset (Ablavar) and Gadobenate (MultiHance)

Question #1 Does your practice perform

Blood Pool Imaging? 1. Yes, frequently 2. Occasionally, for specialized uses 3. No, but it seems intriguing … 4. No, because I don’t understand how

to do it 5. No, because I don’t really see any

benefit

Gd Blood Pool Agents

• Either bind albumin, or macro-aggregates • Contrast stays intravascular (vs. ECF) • Increased temporal window for imaging

- Higher resolution - ECG gating

• Single BP agent approved in USA (2008) = Gadofosveset Trisodium

- Ablavar - Lantheus - Initially “Vasovist” in EU – Bayer - Developmental name “MS-325” - EPIX

Gadofosveset • Linear Gd Chelate • Added side chain – 80-85% binding albumin • Increased relaxivity (r1 and r2)

- ~3-5x r1 of conventional Gd

• Increased intravascular residence - Intravascular t1/2 ~ 30 min

Gadolinium chelate

Diphenylcyclohexyl moiety

Phosphate diester bridge

Adapted from Leiner T et al, eds. Clinical Blood Pool MR Imaging.

ABLAVAR® [package insert]. North Billerica, MA: Lantheus Medical Imaging, Inc.; 2009.

MRA with BPA (Gadofosveset) • First pass –similar to conventional Gd

- Dose 0.03 mmol/kg (vs. standard 0.1 mmol/kg)

• Steady state - Begins ~2-5 minutes - Lasts > 30’ - Allows for greater resolution

• Useful for many MRA territories – e.g. peripheral • Venous imaging

- Allows for ECG triggering • Necessary to negate cardiac motion • T. Aorta (esp root) • Coronary arteries

- Allows for large volume coverage

Gadofosveset 0.03 mmol/kg

Elderly M w/claudication 3-station Runoff

First Pass

63-year-old male smoker – Suspected AIOD

Steady State Source Image - 1.0 x 0.9 x 0.9 mm resolution

Plaque easily seen

Axial Reformat

Gadofosveset 0.03 mmol/kg – Steady State (Blood Pool)

BP Agents T. Aorta • Early uses to aimed at coronary imaging

- “Whole Heart” coronary imaging

Kelle, Thouet, Tangcharoen, Nassenstin, Chiribiri, Paetsxh, Schnackernburg, Rarkhausen, Fleck, Nagel. Med Sci Monit. 2007 Nov;13(11):CR469-474.

Non-contrast Gadofosveset

Steady State Technique Adapted to Imaging Thoracic Aorta

• Naehle et al.+ 2009, University Bonn • Single dose gadofosveset • First pass and steady state – 25 pts • Congenital and acquired diseases thoracic

vasculature • Steady State – ECG gated, 3D IR, 6-8 min,

1.0 x 1.0 x 2.0 mm true resolution

+ Naehle, C. P., Müller, A., Willinek, W. A., Meyer, C., Hestermann, T., Gieseke, J., Schild, H., et al. (2009). First-pass and steady-state magnetic resonance angiography of the thoracic vasculature using gadofosveset trisodium. JMRI, 30(4), 809–816. doi:10.1002/jmri.21919

Naehle et al. - Aneurysm

Naehle, et al. JMRI, 30(4), 809–816. doi:10.1002/jmri.21919

First Pass Steady State

Naehle et al.

• First Pass – higher signal • Steady State – sharper, less

interobserver variability in diameter measurement

Naehle, et al. JMRI, 30(4), 809–816. doi:10.1002/jmri.21919

UW Practice • Many Cases of Aortic Pathology • Congenital

- Bicuspid AOV - Marfan’s - CHD

• Acquired - Aneurysm - Dissection

• Adapted Bonn technique to clinical practice

Example

• 32 y/o Male with Marfan’s • s/p Type A Dissection, Bentall and St. Jude • 0.04 mmol/kg gadofosveset

- 15 cc @ 1.0 cc/sec • 5 channel cardiac coil • 1.5T

First Pass Gadofosveset

1st Pass Vol Rend

1st Pass MIP

Steady State ECG-gated Gadofosveset Delayed Phase - Like Gated CT

Good (Best?) for accurate measurement aortic size

First Pass Steady State

Steady State ECG-gated Gadofosveset Delayed Phase - Looks like gated CT

Significant improvement in resolution ~ 1 x 1 x 1 mm

Source Images Obl Sag Axial MPR s

Example

• 21 y/o Male with chronic respiratory sx • Abnormal CXR • Suspicion of arch anomaly • 0.03 mmol/kg gadofosveset• 5 channel cardiac coil • 1.5T

Chest X-Ray Right Arch, ? Tracheal Narrowing

First Pass Ablavar MIP – Double Aortic Arch - Atretic left – Vascular Ring

Delay SS Ablavar Source Images Delay SS Ablavar Source Images

Delay SS Ablavar Source Images Delay SS Ablavar Axial Reformats

Delay SS Ablavar MIPs Double Aortic Arch Atretic left

Double Aortic Arch - Atretic Left 1st pass vs. gated SS

1st pass SS

1st pass

SS

Technique Useful

• Following up aortic disease • Serial measurements important

- Often done with Echo or CT • Acoustic window/angle problematic Echo • Radiation dose/motion with CT

• ECG-gating necessary, esp closer to root

- Non-gated CE-MRA blurred

Work 2010 – Ascending Aorta

Potthast, S., Mitsumori, L., Stanescu, L. A., Richardson, M. L., Branch, K., Dubinsky, T. J., & Maki, J. H. (2010). JMRI, 31(1), 177–184. doi:10.1002/jmri.22016

3D Nav Gated SSFP vs. CE-MRA

Also saw worse interobserver variability CE-MRA *Need ECG gating – esp close to root …

Example

• 15 y/o Male with ? Marfan s • Possible dilated Ao root by echo • 0.03 mmol/kg gadofosveset • 5 channel cardiac coil• 1.5T

Steady State ECG-gated Gadofosveset Mild Asc Ao Aneurysm

Steady State ECG-gated Gadofosveset Mild Asc Ao Aneurysm – STJ Effaced

First Pass Steady State

Steady State ECG-Gated Gadofosveset Mild Asc Ao Aneurysm – STJ Effaced

First Pass Nav SSFP Gadofosveset SS

Shown nav SSFP better than 1st pass Steady State ? better than nav SSFP … but need to do the study (as per coronary – more SNR; also – time efficient for large volumes)

Technique Simple • Easy free breathing add-on to CE-MRA • Requires cardiac package/ECG gating • Takes 5-8 minutes • Resolution sufficient for good reformats –

- Axial looks very “CTA”-like - More “approachable” to clinicians used to CT

• While standard Gd ECF agents not “blood pool”, they too can work (if fast)

- We have used gadobenate (MultiHance)

35 M s/p Ross Age 8, Replacement Asc AO w/reimplantion Coronary Arteries Age 28

30 mm Sinus of Valsalva Aneurysm

SS 5’ after 0.1 mmol/kg MultiHance

35 M s/p Ross Age 8, Replacement Asc AO w/reimplantion Coronary Arteries Age 28

30 mm Sinus of Valsalva Aneurysm

1st Pass CE-MRA SS 5’ after 0.1 mmol/kg MultiHance

35 M s/p Ross Age 8, Replacement Asc AO w/reimplantion Coronary Arteries Age 28

30 mm Sinus of Valsalva Aneurysm

1st Pass CE-MRA SS 5’ after 0.1 mmol/kg MultiHance

35 M s/p Ross Age 8, Replacement Asc AO w/reimplantion Coronary Arteries Age 28

Repeated Ablavar 6 mo later

SS 5’ after 0.1 mmol/kg MultiHance SS 5’ after 0.03 mmol/kg Ablavar

Question #2 Do you think Blood Pool Imaging

has a future in body MRA? 1. Yes, and we should be using it more 2. Yes, but it is a very “niche” imaging

technique only for experienced centers

3. No, it’s too complicated and/or expensive (time and $)

4. No, doesn’t add anything to what we already have

Conclusion (1/2) • Accurate and reproducible metrics of

the aorta are extremely important • ECG-gating essential

- Decreased blur - Less interobserver variability

• Blood pool agents an appealing solution

- Simple add on, especially if doing 1st pass MRA anyway

- Free breathing – greater resolution/detail

Conclusion (2/2)

• Our institution has seen good clinical success/acceptance SS MRA

- Implementing 90+% thoracic aortic MRA’s - > 100 cases to date

• Need studies to compare: - Nav SSFP vs. SS Blood Pool MRA - SS Blood Pool MRA gadofosveset vs. “other ECF”