I-123 MIBG Imaging: Collimators & H/M Ratio

The same patient can yield a heart-to-mediastinum ratio of 1.4 on one gamma camera and 1.8 on another — not because the heart changed, but because the collimator did. I-123 MIBG imaging is deceptively simple to acquire and surprisingly easy to quantify inconsistently. The reason is physics: a small fraction of high-energy I-123 photons penetrate collimator septa, and how you handle them decides whether your numbers mean anything across cameras and over time. ^{1, 5, 6}

Introduction

Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that is taken up and stored by sympathetically innervated tissue and by tumors of neuroendocrine origin. Labeled with iodine-123, it supports two very different clinical questions. In cardiology, I-123 MIBG measures cardiac sympathetic innervation through the heart-to-mediastinum (H/M) ratio and washout rate, which carry prognostic weight in heart failure. In pediatric oncology, I-123 MIBG maps neuroblastoma and related tumors, and the extent of MIBG-avid disease is scored to guide risk stratification and response assessment. ^{2, 3, 4, 8}

Both applications live or die on quantification. An H/M ratio is only useful if it is comparable to the value that generated a published threshold. A neuroblastoma score is only useful if the images faithfully show the disease. And both depend on getting the underlying physics right — the collimator, the energy windows, the acquisition timing, and the thyroid blockade that protects the patient. This article walks through the imaging physics of I-123 MIBG and the practical decisions that keep the numbers honest. DRPS supports nuclear medicine programs with this work through PET/CT and nuclear medicine physics and accreditation support across Florida, Maryland, Virginia, Washington DC, California, and Nevada.

Topic Explanation

The tracer and its two jobs

MIBG enters cells through the norepinephrine transporter and is stored in intracellular granules without being metabolized, so its distribution reflects the density and function of sympathetic nerve terminals. In the healthy heart, that means dense, uniform uptake in the left ventricular myocardium. In heart failure and certain neurodegenerative conditions, sympathetic denervation reduces cardiac uptake, which the H/M ratio captures as a lower number. ^{3, 4}

In neuroblastoma, MIBG concentrates in tumor cells that express the same uptake machinery. Because roughly 90% of neuroblastomas are MIBG-avid, whole-body I-123 MIBG scintigraphy — increasingly with SPECT/CT — is a mainstay of staging and response assessment, and the burden of avid disease is graded with validated scoring systems. ^{2, 8, 9, 10}

Why the label isotope matters

The choice of iodine-123 over iodine-131 for imaging is a physics decision. I-131 emits a high-energy 364 keV gamma and energetic beta particles, which make it a therapy isotope with poor imaging characteristics and high patient dose. I-123 emits a 159 keV photon that is nearly ideal for a modern gamma camera and delivers far less dose, with a physical half-life of about 13.2 hours that matches the same-day early-and-delayed imaging protocol. ^{1, 2}

The catch is that I-123 is not a pure 159 keV emitter. Its decay also produces a small yield of high-energy photons, most notably near 529 keV. Those photons are the source of nearly every quantification headache in MIBG imaging. ^{1, 5}

Key Technical Principles

Septal penetration: the core problem

A low-energy collimator is designed for 140 keV Tc-99m. Its septa are thin, optimized to stop 140–159 keV photons while maximizing sensitivity. When a ~529 keV I-123 photon arrives, those thin septa are largely transparent to it. The photon can pass through septal lead, scatter, and deposit energy that lands inside the 159 keV acquisition window — a spurious count recorded at the wrong location.

The clinical consequence is specific and directional. High-activity organs near the heart — the liver and lungs — become sources of penetrating high-energy photons that add counts to the mediastinal reference region and the myocardial region alike. Because the H/M ratio is a ratio of two regions, this contamination compresses the ratio toward 1.0, systematically lowering measured H/M on a low-energy collimator. ⁵

The fix is a medium-energy (ME) collimator, whose thicker septa reject most of the high-energy penetration at the cost of some sensitivity and resolution. The effect is large and reproducible:

Collimator	Septa	Representative late H/M ratio (same patients)	Effect on quantification
Low-energy high-resolution (LEHR)	Thin, tuned for 140 keV	≈ 1.41 ± 0.18	Septal penetration from liver/lung lowers H/M
Medium-energy (ME)	Thick, rejects high-energy photons	≈ 1.80 ± 0.41	Cleaner mediastinal reference; higher, truer H/M

The values above are from an intrapatient comparison in which the same patients were imaged with both collimators; roughly 90% of the LEHR-versus-ME difference was attributable to high-energy penetration and liver scatter. ⁵ This is why current cardiac standardization guidance favors a medium-energy collimator for quantitative H/M work. ³

Defining the H/M ratio

The H/M ratio is computed from a planar anterior chest image. A region of interest is drawn over the left ventricle, and a rectangular reference region is placed in the upper mediastinum. The ratio is:

H/M = \frac{c ˉ _{heart}}{c ˉ _{mediastinum}}

where $\overset{c}{ˉ}$ is the mean counts per pixel in each region. As a worked illustration, suppose the myocardial region averages 228 counts per pixel and the mediastinal region averages 150 counts per pixel on a delayed image:

H/M = \frac{228}{150} = 1.52

On the ADMIRE-HF camera and collimator, an H/M below the 1.60 lower limit of normal placed a heart-failure patient in the higher-risk group. ⁴ But 1.52 measured on a low-energy collimator and 1.52 measured on a medium-energy collimator are not the same physiologic quantity — which is the entire motivation for cross-calibration.

Washout rate

Sympathetic drive also shows up in how quickly MIBG leaves the heart. The washout rate compares early (roughly 15-minute) and delayed (roughly 4-hour) images:

WR = \frac{H _{early} - H _{late}^{*}}{H _{early}} \times 100%

where the late myocardial counts $H_{late}^{*}$ are corrected for physical decay and, in many conventions, for background using the mediastinal region. An accelerated washout indicates increased sympathetic tone. The exact formula — whether decay correction and background subtraction are applied — varies by center, so a washout value must be interpreted against the same convention that produced its reference range rather than a single universal cut-off. ³

Cross-calibration: making H/M portable

Because the measured H/M depends on the collimator and camera, a value from one site is not interchangeable with a published threshold from another. Multicenter phantom studies solved this by acquiring a standard chest phantom with a known "true" H/M on many camera-collimator combinations and deriving conversion coefficients. Low-energy systems required conversion coefficients around 0.55–0.75, and medium-energy systems around 0.83–0.95, with a widely used medium-energy-referenced standardization coefficient near 0.88. Applying the coefficient transforms a site's raw H/M into a standardized value so that thresholds — such as the low, intermediate, and high-risk strata below 1.60, 1.60–2.19, and 2.20 and above — can be applied consistently. ^{6, 7}

Clinical Impact

Cardiac imaging and risk

The prognostic value of cardiac I-123 MIBG was established by the ADMIRE-HF study, which enrolled patients with New York Heart Association class II–III heart failure and left ventricular ejection fraction at or below 35%. The late planar H/M ratio, measured about four hours after injection, separated risk cleanly: patients with H/M below 1.60 had roughly a 37% two-year event rate, versus about 15% for those at or above 1.60. ⁴ A subsequent analysis showed the H/M ratio added prognostic information across the range of ejection fractions, not merely restating what the EF already told clinicians. ¹²

That prognostic power is only realized if the H/M ratio is measured with a quantification-appropriate technique — medium-energy collimator, consistent energy windows, standardized ROI placement, and cross-calibration to a comparable reference. A study acquired casually on a low-energy collimator will read systematically low and can misclassify a patient's risk.

Neuroblastoma staging and response

In pediatric oncology, whole-body I-123 MIBG scintigraphy grades the extent of avid disease. Two validated semiquantitative systems dominate. The Curie score divides the body into ten anatomic regions, each scored 0–3 for the extent of MIBG-avid lesions. The SIOPEN score uses twelve skeletal regions, each scored 0–6. Both have been validated in large cooperative-group trials, where a higher post-induction score predicts significantly worse event-free survival in high-risk neuroblastoma. ^{9, 10} The physics priorities shift here from a single ratio to faithful lesion detection: adequate counts, medium-energy collimation, SPECT/CT for anatomic localization, and consistent scoring against the same image quality.

Practical Optimization Tips

Getting the acquisition right

Use a medium-energy collimator for quantitative work. For H/M ratios especially, the systematic bias of a low-energy collimator is large enough to change risk classification. ^{3, 5}
Set energy windows deliberately. Center a 15–20% window on the 159 keV photopeak; be aware that scatter and high-energy down-scatter contribute to the window, which is another argument for medium-energy collimation.
Standardize ROI placement. Use a consistent myocardial region and a defined mediastinal reference (typically an upper-mediastinal box). Small, reproducible regions reduce operator variability in the ratio.
Fix the timing. Acquire early (~15 min) and delayed (~3.5–4 h) planar anterior images so both the H/M ratio and washout rate are defined against their reference ranges. ^{3, 4}

Making numbers comparable

Cross-calibrate. Acquire a standardization phantom and derive your system's conversion coefficient so H/M values map to the standardized scale before applying any published threshold. ^{6, 7}
Report the method with the number. An H/M ratio without its collimator, window, and calibration is not interpretable by anyone else.
Trend consistently. For serial studies in the same patient, hold the camera, collimator, windows, and processing constant.

Protecting the patient

Block the thyroid. Give a thyroid-blocking agent — potassium iodide equivalent to about 100 mg iodide, or potassium perchlorate around 400 mg in adults, weight-adjusted in children — at least one hour before injection, and continue per protocol. ^{2, 11}
Screen interfering drugs. Many agents (some tricyclic antidepressants, labetalol, sympathomimetics) reduce MIBG uptake and should be withheld for several biological half-lives where clinically appropriate. ¹¹
Weight-base pediatric activity. Follow the EANM pediatric dosage card with its specified minimum administered activity rather than scaling an adult dose by eye. ⁸

Regulatory Considerations

I-123 MIBG imaging sits under the same medical-use and radiation-safety framework as any unsealed byproduct-material study, plus the specific requirements of the drug label. For the cardiac application, AdreView (iobenguane I-123) is an FDA-approved radiopharmaceutical, and its prescribing information specifies the adult administered activity of 370 MBq (10 mCi), the thyroid-blockade requirement, imaging timing, and the interpretive use of the H/M ratio. ¹¹ Off-label or investigational protocols, and the compounding or handling of the agent, must remain consistent with the facility's radioactive material license.

Medical use of I-123 is governed by 10 CFR Part 35 (or the equivalent Agreement State program) and the radiation protection standards of 10 CFR Part 20, including patient-specific dose considerations for pediatric imaging. For accreditation, the ACR and the Intersocietal Accreditation Commission expect documented gamma-camera performance testing, appropriate collimator use, and a quality-control program that supports quantitative imaging. Guideline-level expectations for acquisition and quantification come from the EANM and SNMMI procedure guidelines for MIBG tumor and cardiac imaging and the EANM neuroblastoma imaging guideline. ^{2, 3, 8}

For DRPS clients, the jurisdictional map is the usual one: Florida, Maryland, Virginia, California, and Nevada are NRC Agreement States administering their own equivalent rules, while Washington, DC is regulated directly by the NRC. The medical physicist's role is to make the quantitative program defensible — collimator selection, energy-window verification, cross-calibration, and documented camera QC — so that an H/M ratio or neuroblastoma score is both clinically valid and accreditation-ready. See our guides on gamma-camera collimator selection and SPECT/CT quality control for the underlying QC.

Frequently Asked Questions (FAQs)

Why do I-123 MIBG studies need a medium-energy collimator?

I-123 emits a small fraction of high-energy photons near 529 keV in addition to its 159 keV imaging photon. Those high-energy photons penetrate the thin septa of a low-energy collimator and add spurious counts, especially from the liver and lungs, which inflate mediastinal and myocardial regions of interest. A medium-energy collimator has thicker septa that reject most of this penetration, giving a more accurate heart-to-mediastinum ratio. In one intrapatient comparison, the late H/M ratio was about 1.41 with a low-energy collimator versus 1.80 with a medium-energy collimator in the same patients.

What is the heart-to-mediastinum (H/M) ratio?

The H/M ratio is a semiquantitative index of cardiac sympathetic innervation. It is the mean counts per pixel in a region of interest over the heart divided by the mean counts per pixel in a mediastinal reference region, measured on a planar anterior image, usually about 3.5 to 4 hours after injection. A lower H/M ratio indicates reduced cardiac sympathetic activity and, in heart failure, a higher risk of cardiac events.

What H/M ratio is considered abnormal?

In the ADMIRE-HF study, a late H/M ratio below 1.60 identified patients at higher risk, with a roughly 37 percent two-year event rate versus about 15 percent for patients at or above 1.60. The 1.60 threshold is specific to the camera and collimator used in that study, which is exactly why cross-calibration to a standardized value matters before applying any published cut-off locally.

Why does thyroid blockade matter for MIBG?

MIBG is labeled with iodine, and a small amount of free radioiodine is always present or generated in vivo. Without blockade, that free iodide concentrates in the thyroid and delivers unnecessary dose. Patients receive a thyroid-blocking agent, such as potassium iodide or potassium perchlorate, at least one hour before the MIBG injection, and blockade is continued per protocol to protect the thyroid.

How is MIBG uptake scored in neuroblastoma?

Two validated semiquantitative systems are used. The Curie score divides the body into ten anatomic regions, each scored 0 to 3. The SIOPEN score uses twelve skeletal regions, each scored 0 to 6. Both grade the extent and intensity of MIBG-avid disease, and the post-induction score is prognostic for outcome in high-risk neuroblastoma.

Can H/M ratios be compared across different cameras?

Not directly. Because the collimator and camera strongly affect the measured H/M ratio, a value from one system is not interchangeable with another. Multicenter phantom work established conversion coefficients that transform a site's H/M ratio to a standardized medium-energy-equivalent value, near 0.88 for many systems, so that published thresholds can be applied consistently. A cross-calibration phantom acquisition is the practical tool for this.

What administered activity is used for cardiac I-123 MIBG?

For the cardiac AdreView application in adults, the prescribing information specifies 370 MBq, or 10 mCi, administered intravenously, with early imaging around 15 minutes and delayed imaging around 3.5 to 4 hours. Pediatric neuroblastoma activities are weight-based, following the EANM pediatric dosage card, with a specified minimum administered activity.

Key Takeaways

Septal penetration is the central issue. I-123's high-energy photons near 529 keV pass through low-energy collimator septa and distort quantification. ^{1, 5}
Use a medium-energy collimator for quantitative H/M work. The same patients read ~1.41 on LEHR versus ~1.80 on ME — a difference large enough to change risk classification. ⁵
H/M below 1.60 flagged higher risk in ADMIRE-HF, but that threshold is camera- and collimator-specific and must be applied through cross-calibration. ^{4, 6}
Cross-calibrate to a standardized scale. Conversion coefficients near 0.88 for medium-energy systems make H/M ratios portable across sites. ^{6, 7}
Neuroblastoma uses Curie (10 regions, 0–3) and SIOPEN (12 regions, 0–6) scoring, both prognostic post-induction. ^{9, 10}
Protect the patient. Block the thyroid at least an hour before injection, screen for interfering drugs, and weight-base pediatric activity. ^{8, 11}

Conclusion

I-123 MIBG is a powerful tracer that rewards attention to physics and punishes shortcuts. Because a small fraction of high-energy photons penetrates collimator septa, the collimator, energy windows, and cross-calibration you choose determine whether a heart-to-mediastinum ratio or a neuroblastoma score is comparable to the literature and to the patient's own prior study. The clinical stakes are real: an H/M ratio drives risk stratification in heart failure, and a MIBG score guides therapy in high-risk neuroblastoma. Getting the acquisition and quantification right — medium-energy collimation, standardized regions, documented calibration, and thyroid protection — is exactly the medical-physics work that turns a pretty image into a defensible number.

How DRPS Can Help

Diagnostic Radiation Physics Services supports nuclear medicine programs that perform I-123 MIBG and other quantitative studies with gamma-camera and SPECT/CT acceptance and performance testing, collimator and energy-window verification, H/M cross-calibration support, protocol review, and accreditation support. Our PET/CT and nuclear medicine physics and medical physicist consulting services are performed by board-certified medical physicists.

DRPS supports facilities across our service locations, including Florida, Maryland, Virginia, Washington DC, California, Nevada, New York, Pennsylvania, New Jersey, and Delaware.

A quantitative imaging program is only as good as its worst uncontrolled variable — and in MIBG imaging, that variable is usually the collimator.

Related Resources

References

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